Extracellular vesicles nyob rau hauv lub raum thiab lawv qhov chaw kho mob muaj peev xwm nyob rau hauv cov kab mob raum
Mar 03, 2023
Extracellular vesicles (EVs), xws li exosomes thiab microvesicles, yog cell-derived lipid bilayer membrane hais, uas xa cov ntaub ntawv los ntawm cov cell cell mus rau cov neeg tau txais. EVs tau koom nrog ntau yam txheej txheem lom neeg suav nrog kev hloov kho ntawm lub cev tiv thaiv kab mob, kev sib txuas lus ntawm tes-rau-cell, thrombosis, thiab cov ntaub so ntswg rov ua dua tshiab. Ntau hom kab mob hauv lub raum paub tias tso tawm EVs nyob rau hauv physiologic nrog rau cov kab mob pathologic, thiab cov kev tshawb fawb tsis ntev los no tau pom tias EVs muaj lub luag haujlwm ntawm pathophysiologic sib txawv.kab mob raum. Muab qhov kev nce qib tsis ntev los no hauv EV kev cais tawm thiab kev tshuaj ntsuam xyuas, ntau cov kev tshawb fawb tau qhia txog kev kuaj mob thiab kho lub peev xwm ntawm EVs hauv ntau yam.kab mob raum, xws li mobmob raum, polycystic kab mob raum, mob raum mob, kidney hloov, thiab lub raum cell carcinoma. Qhov kev tshuaj xyuas no hloov kho cov kev soj ntsuam tsis ntev los no thiab kev tshawb pom ntawm lub luag haujlwm ntawm EVs hauvkab mob raumthiab highlights lubmuaj peev xwm siv tshuaj kho mob ntawm EVsraws li cov tshiab diagnostics thiab kho.
Ntsiab lus: Biomarkers, Exosomes, Extracellular vesicles,Kev tiv thaiv, Kab mob raum, Microvesicles
Taw qhia
Extracellular vesicles (EVs) xa mus rau tag nrho cov endogenously tsim membrane-bound vesicles uas tau tso tawm los ntawm cov hlwb mus rau hauv lub extracellular qhov chaw. EVs muaj ntau yam molecules, xws li DNA, messenger RNA (mRNA), proteins, lipids, thiab microRNAs (miRNAs). Cov subtypes sib txawv ntawm EVs tau piav qhia suav nrog exosomes, microvesicles lossis microparticles, apoptotic lub cev, exosomes, thiab endosomes raws li lawv cov keeb kwm, qhov loj me, cov ntsiab lus, thiab biogenesis (Table 1). Hauv kev nkag siab nqaim, EVs feem ntau xa mus rau exosomes lossis microvesicles. Hauv kev tshuaj xyuas no, peb yuav siv lub ntsiab lus dav dav 'EVs' los tsom rau exosomes thiab microvesicles vim muaj cov yam ntxwv sib tshooj ntawm cov subtypes sib txawv. EVs tau pib tshawb pom ntau dua 30 xyoo dhau los, tab sis nws tau xav tias lawv lub luag haujlwm ntawm lub cev tsuas yog txwv rau kev tso tawm ntawm cov kab mob hauv nruab nrog cev lossis daim nyias nyias ntawm cov hlwb. Txawm li cas los xij, kev nce qib tsis ntev los no tau pom tias EVs tau koom nrog ntau yam txheej txheem lom neeg xws li kev tiv thaiv kab mob, hemostasis, thiab cov ntaub so ntswg proliferation / regeneration, uas tuaj yeem cuam tshuam rau kev loj hlob thiab kev tsim ntawm lub cev. EVs kuj pom dav dav hauv cov kab mob pathologic. Lawv lub xub ntiag nyob rau hauv ib qho dej hauv lub cev nthuav dav lub luag haujlwm kuaj mob ntawm EVs ua biomarkers hauv ntau hom kab mob. EVs kuj tseem ua rau muaj kev kis kab mob los ntawm kev cuam tshuam rau theem ntawm o, thrombosis, thiab qog nqaij hlav. Ntawm qhov tod tes, EVs tau txais kev kho mob ntau yam ua lub peev xwm kho tsheb raws li lawv lub peev xwm kaw cov protein thiab cov khoom siv caj ces. Hauv kev tshuaj xyuas no, peb yuav tsom mus rau lub luag haujlwm ntawm EVs hauv lub raum physiology thiab cov txheej txheem kab mob nrog rau lawv cov peev xwm siv tau raws li kev kuaj mob thiab kev kho mob hauv ntau yam.kab mob raum.
Lub luag haujlwm physiologic ntawm extracellular vesicles hauv lub raum
Nyob rau hauv physiologic tej yam kev mob, lub luag haujlwm tseem ceeb ntawm EVs yog tshem tawm cov khoom tsis xav tau los ntawm cov tswv tsev cell.EVs tseem tuaj yeem hloov cov ntaub ntawv tseem ceeb lom rau lawv cov hlwb los ntawm kev xa cov khoom siv noob caj noob ces, proteins, lipids, thiab receptors. Kev xa tawm ntawm RNAs lossis miRNAs tuaj yeem muaj txiaj ntsig zoo rau cov neeg tau txais cov hlwb los ntawm kev rov ua dua lawv cov yam ntxwv ntawm caj ces. Hauv qab no, peb yuav tham txog kev nthuav dav txog kev ua haujlwm lom neeg ntawm EVs hauv lub raum physiology (Daim duab 1A).
Daim duab 1. Lub luag hauj lwm ntawm extracellular vesicles (EVs) nyob rau hauv ib txwm ob lub raum thiab raum kab mob. (A) EVs kho kom haum xeeb ntawm kev sib txuas lus ntawm tes mus rau ntawm tes, hloov kho cellular homeostasis, electrolyte / dej sib npaug, tubular regeneration, thiab inflammatory reactions hauv lub raum ib txwm. (B) EVs cuam tshuam txog kev kis kab mob los ntawm kev ua kom muaj qhov mob thiab ua rau tubulointerstitial fibrosis lossis glomerular epithelial-mesenchymal hloov pauv (EMT). EVs kuj tseem tuaj yeem koom nrog hauv pathogenesis ntawm lub raum cell carcinoma (RCC) thiab lub raum allograft rejection.
Ag, antigen; CD, sau cov kav dej; DC, dendritic cell; DT, distal tubule; ENaC; epithelial sodium channel; PT, lub cev sib npaug; TEC, tubular epithelial hlwb.
Hloov kho los ntawm tsab xov xwm ntawm Kwon et al. (Korean J Intern Med 2019; 34:470-479) raws li Creative Commons License.
Homeostasis thiab cell ciaj sia
Ib lub luag haujlwm tseem ceeb tshaj plaws ntawm EVs yog nyob rau hauv kev tshem tawm cov khoom siv tshuaj lom hauv lub cev mus rau hauv qhov chaw extracellular. Raws li cov hlwb dhau los ntawm ntau cov txheej txheem lom neeg, lawv tsim cov organelles puas thiab cellular pov tseg, uas tuaj yeem ua rau muaj kev ntxhov siab ntawm cellular ua rau cell tuag lossis mob. Eukaryotic hlwb tau tsim ib qho kev tiv thaiv tus kheej rau kev tshem tawm cov khib nyiab hauv lub cev - kev tso tawm ntawm EVs rau hauv qhov chaw ntxiv. Nyob rau hauv txoj kev no, cov hlwb tuaj yeem tshem tawm cov teeb meem chromosomal DNA tawg los ntawm exosomes. Qhov inhibition ntawm cov txheej txheem no tuaj yeem ua rau lub cev tsis muaj zog tiv thaiv kab mob, DNA puas, thiab apoptosis hauv tib neeg lub cev.Lub raumcov hlwb kuj raug rau kev nyuaj siab lom neeg. Nyob rau hauv cov xwm txheej hypoxic, lub raum tubular hlwb proactively tsub kom tus nqi ntawm exosome secretion thiab hloov cov muaj pes tsawg leeg ntawm exosomes kom tau raws li cov kev xav tau lom. EV uptake mus rau hauv cov neeg tau txais cov hlwb kuj yog ib qho tseem ceeb ntawm cov txheej txheem lom neeg hauv kev sib txuas lus. Cov txheej txheem feem ntau ntawm cov cellular uptake yog endocytosis uas cov EVs tau nkag los ntawm cov neeg tau txais cov hlwb. Qhov sib npaug ntawm EV tso tawm thiab kev txhawb nqa yog nyob ntawm qhov mob ntawm lub cev ntawm niam txiv / tus neeg txais cov hlwb, hom niam txiv / cov neeg txais lub hlwb, thiab kev lees paub ntawm ligands / receptors ntawm EVs thiab cov hlwb tau txais.
Inflammation / immunomodulation
EVs yog ib qho me me ntawm lawv cov niam txiv lub hlwb, yog li lawv cov kev tiv thaiv kab mob ua haujlwm tseem ceeb nyob ntawm lawv cov keeb kwm thiab microenvironment lawv cov niam txiv cov hlwb raug nthuav tawm. Piv txwv li, EVs los ntawm cov hlwb dendritic tuaj yeem ua haujlwm raws li cov tshuaj tiv thaiv kab mob los ntawm kev nthuav qhia ncaj qha ntawm peptide-loj histocompatibility complexes (MHC) complexes rau T hlwb. Cov peptide-MHC complexes tuaj yeem raug xa mus rau lwm lub hlwb uas tau txais, tsis ncaj qha nthuav tawm antigens, thiab tom qab ntawd ua rau lub cev tiv thaiv kab mob. Ntawm qhov tod tes, EVs zais los ntawm cov qog hlwb tuaj yeem kho qhov kev tiv thaiv kab mob tiv thaiv kab mob los ntawm kev hloov cov monocytes thiab T hlwb rau tolerogenic subtypes, inhibiting qhov sib txawv ntawm monocytes, los yog inducing apoptosis ntawm bystander T hlwb, thiaj li hu ua activation-induced cell tuag. . Lub cev lub cev ntawm niam txiv lub hlwb cuam tshuam rau cov ntsiab lus ntawm EVs. Piv txwv li, exosomes muab tau los ntawm cov qog nqaij hlav hypoxic tuaj yeem ua rau muaj kev sib txawv ntau dua thiab kev ua kom cov hlwb myeloid-derived suppressor piv rau exosomes muab los ntawm cov hlwb nyob rau hauv cov xwm txheej normoxic.
Antimicrobial nyhuv
Cov kab mob urinary yog ib txwm raug rau cov kab mob los ntawm sab nrauv ib puag ncig, ua rau muaj kev pheej hmoo siab ntawm cov kab mob urinary. Txawm li cas los xij, feem ntau ntawm cov zis, tshwj tsis yog lub urethra, feem ntau tseem tsis muaj menyuam. Qhov kev tiv thaiv kab mob no yog kho los ntawm ntau yam. Kev lig kev cai, cov teeb meem anatomical, xws li glycoprotein plaque thiab ib txheej ntawm hydrated mucus, nrog rau kev tiv thaiv kev tiv thaiv kab mob los ntawm ntau lub cev tiv thaiv kab mob thiab cov kab mob epithelial hauv ob sab phlu, tau suav hais tias yog cov cuab yeej tiv thaiv tseem ceeb. Tsis ntev los no, EVs tau pom los ua lub luag haujlwm tseem ceeb tiv thaiv kab mob hauv cov zis. Ib txoj kev tshawb fawb proteomic tau pom tias muaj cov protein ntau hauv lub cev tiv thaiv kab mob suav nrog calprotectin thiab lysozyme C hauv cov zis EVs tuaj yeem kho cov tshuaj tiv thaiv kab mob. Txawm hais tias autophagy yog ib qho kev tiv thaiv zoo ntawm tes los tshem tawm cov kab mob txawv teb chaws, qee cov kab mob tau hloov kho cov txheej txheem tiv thaiv kom kov yeej autophagy los ntawm neutralizing lysosomal pH. Kev kawm los ntawm Miao et al. qhia tau hais tias lub zais zis epithelial hlwb tuaj yeem kov yeej qhov tshwm sim no los ntawm exosomes - los ntawm kev tshem tawm cov kab mob exosome-encased los ntawm qhov chaw intracellular.
Lub raum regeneration / kho
Mesenchymal qia hlwb (MSCs) yog qhov paub zoo rau lawv cov kev tsim kho tshiab thiab rov kho dua tshiab hauv cov kabmob sib txawv nrog raulub raum.Txawm li cas los xij, lub peev xwm rov kho dua ntawm MSCs yog kho los ntawm EVs ntau dua li qhov sib txawv ntawm MSCs lawv tus kheej. MSC-derived EVs muaj ntau hom tshuaj tiv thaiv kab mob antioxidants thiab kev loj hlob yam tseem ceeb los txhawb kev sib txawv ntawm cov neeg nyob hauv progenitor hlwb. Kev xa cov khoom siv caj ces zoo li DNA, miRNAs, lossis mRNAs los ntawm EVs kuj tuaj yeem qhia txog cov peev txheej ntawm niam txiv MSCs rau cov neeg tau txais cov hlwb. Hauv kev tshawb fawb los ntawm Ranghino li al., glomerular MSC-derived EVs mediated tubular epithelial cell regeneration thiab alleviated ischemic mob raum raug mob (AKI) los ntawm kev hloov mRNAs thiab miRNAs nrog cov muaj peev xwm tiv thaiv cov teebmeem.
Nyem rau Yuav Ua Li Cas Cistanche
NUG ntxiv:david.deng@wecistanche.com
Hemostasis thiab platelet aggregation
Ntau cov ntawv tshaj tawm tau tshaj tawm cov khoom coagulant ntawm plasma EVs hauv tib neeg. EVs keeb kwm los ntawm platelets, endothelial hlwb, los yog leukocytes tau pom tias muaj feem cuam tshuam rau hauv chav kawm ntawm hemostasis. Cov EVs no tuaj yeem pib cov txheej txheem coagulation los ntawm kev nthuav tawm phosphatidylserine (PS) ntawm lawv qhov chaw kom tso cai rau cov chaw sib txuas rau coagulation yam. Lwm lub tswv yim yog los ntawm kev qhia cov ntaub so ntswg ntawm lawv qhov chaw, pib txoj hauv kev extrinsic coagulation thiab ua rau thrombin tawg thiab platelet clot tsim. Kev tshawb fawb los ntawm Yu et al. qhia tias cov neeg mob nrogntshav qab zib raumtus kab mob muaj qib siab dua ntawm PS-expressing microvesicles piv rau cov pab pawg tswj. Lawv kuj pom tias cov qib siab ntawm PS-zoo microvesicles tau cuam tshuam nrog cov xwm txheej hypercoagulable thiab ua rau lub raum tsis zoo. Ib qho kev tshawb pom zoo sib xws tau pom hauv cov neeg mob immunoglobulin A nephropathy.
Tsis ntev los no, ntau qhov kev tshawb fawb tau rov mus xyuas cov cuab yeej pro-coagulation ntawm EVs vim tias muaj kev txhim kho hauv kev sau cov ntshav, kev npaj plasma, thiab EV cais tawm. Interestingly, plasma EVs cais los ntawm cov tib neeg noj qab haus huv txhawb fibrinolysis ntau dua coagulation. Qhov sib txawv no qhia txog lub luag haujlwm tsis zoo ntawm EVs hauv cov txheej txheem hemostasis, uas nyob ntawm microenvironment. Tsis tas li ntawd, kev npaj EV kom zoo yog qhov tseem ceeb rau kev nkag siab zoo ntawm lawv lub luag haujlwm hauv tib neeg lub cev.
Vessel kev ncaj ncees thiab revascularization
Endothelial cell-derived EVs pab tswj cov hlab ntsha kev ncaj ncees thiab txhawb cov vascular endothelial cell ciaj sia los ntawm kev tshem tawm cov xov tooj ntawm tes-tuag thiab tso tawm ntau ntxiv los ntawm vascular endothelial hlwb. Nyob rau hauv cov hlab ntsha puas, platelet-derived EVs induce lub adhesion ntawm endothelial hlwb mus rau extracellular matrix, uas pab lub regeneration ntawm endothelium thiab attenuates vascular permeability.
Cov qog-derived EVs tau paub zoo rau lawv cov khoom siv tshuaj angiogenetic, tab sis EVs tuaj yeem ua rau muaj cov kab mob angiogenesis nyob rau hauv physiologic tej yam kev mob. Endothelial cell-derived EVs modulate angiogenesis los ntawm kev txhawb nqa endothelial cell invasion thiab capillary zoo li cov qauv tsim. Tsis ntev los no, kev hloov pauv ntawm qee cov miRNAs, suav nrog miR-126 lossis miR-124, siv cov endothelial cell-derived EVs thiab cov neeg tau txais cov hlwb endothelial tau pom tias muaj lub luag haujlwm tseem ceeb hauv angiogenesis. MSC-induced EVs kuj induce angiogenesis los ntawm kev hloov cov proteins xws li phosphorylated signal transducers thiab activators ntawm transcription-3 los yog nuclear factor-kB pathway-associated proteins, ua rau transcription ntawm proangiogenic proteins. MSC-derived EVs tuaj yeem hloov pauv ntau yam kev loj hlob xws li kev loj hlob ntawm epidermal thiab vascular endothelial kev loj hlob mus rau endothelial hlwb txhawb kev angiogenesis. Cov ncauj lus kom ntxaws ntxiv txog cov txheej txheem angiogenetic ntawm EVs los ntawm ntau lub hauv paus ntawm cov cellular tuaj yeem pom hauv tsab xov xwm tshuaj xyuas los ntawm Toodorova li al..
Electrolyte thiab dej sib npaug
Sodium / dej reabsorption yog ib qho ntawm cov haujlwm tseem ceeb ntawm lub raum tubular hlwb. Ob feem peb ntawm filtrated sodium yog reabsorbed nyob rau hauv proximal tubular epithelial hlwb thiab fine-tuning rau sodium, reabsorption tshwm sim nyob rau hauv lub distal tubule thiab sau ducts. Yog li ntawd, kev sib txuas lus sib txuas ntawm qhov sib thooj thiab qhov nruab nrab / kev sib sau cov tubular yog qhov tseem ceeb rau kev saib xyuas kom zoo ntawm electrolyte tshuav thiab tswj ntim. Ib txoj kev tshawb fawb los ntawm Jella et al. qhia tau hais tias exosomes los ntawm cov tubular ze ze tuaj yeem tswj cov epithelial sodium channel kev ua haujlwm nyob rau hauv lub distal tubule thiab sau cov ducts los ntawm exosomal xa ntawm glyceraldehyde 3-phosphate dehydrogenase. Thaum raug vasopressin, cortical sau cov hlab ntsha hauv cov hlab ntsha ua rau muaj cov kab dej aquaporin hauv lawv tus kheej thiab hauv lawv cov exosomes. Cov exosomes no tuaj yeem hloov cov kev ua haujlwm ntawm aquaporin mus rau lwm cov tubular hlwb, ua rau lawv muaj peev xwm thauj dej. Los ntawm kev sib txuas lus inter thiab intracellular kev sib txuas lus ntawm lub raum epithelial hlwb ntawm cov sib txawv nephron ntu, exosomes muab lub luag haujlwm tseem ceeb hauv electrolyte thiab kua dej sib npaug hauv tib neeg lub cev.
Extracellular vesicles raws li kev kho mob ntawm cov kab mob raum
Hauv cov kab mob pathologic, kev tsim cov EVs tau nce ntxiv, pab txhawb kev pib thiab nthuav tawm cov kab mob los ntawm kev tiv thaiv kab mob, thrombogenesis, thiab oncogenesis. Lub luag haujlwm ntxaws ntxaws ntawm lub raum EVs hauv cov kab mob sib txawv tau tham hauv qab no (Daim duab 1B).
Glomerular kab mob
Hauv cov kab mob glomerular siab, tubular puas thiab fibrosis yog cov txheej txheem ua haujlwm ntawm lub raum tsis ua haujlwm. Ib txoj kev tshawb fawb tsis ntev los no los ntawm Jeon et al. tau qhia tias miRNAs hauv EVs tso tawm los ntawm cov raug mob podocytes tuaj yeem ua rau tubular epithelial cell apoptosis, qhia tias muaj peev xwm glomerulotubular crosstalk. Txoj kev tshawb no tseem qhia tau tias miRNA profile hauv EVs los ntawm cov neeg raug mob podocytes txawv ntawm cov uas tsis raug mob podocytes, thiab miRNA ua rau cov neeg raug mob podocytes tuaj yeem tsim cov nyhuv proapoptotic ntawm lub raum tubular epithelial hlwb. Hauv kev mob ntshav qab zib nephropathy, raug rau qib qabzib siab tuaj yeem ua rau EV ntau lawm los ntawm podocytes. Tubular epithelial hlwb uptake cov podocyte-derived EVs thiab tsim tubular fibrosis los ntawm p38 phosphorylation.
Mob raum raug mob
Ib txoj kev tshawb nrhiav miRNA tsis ntev los no tau pom tias cov zis exosomal miRNAs muaj cov yam ntxwv thiab cov khoom ua haujlwm uas nyob ntawm theem AKI. Ob peb exo-miRNAs (miR-16, miR-24, thiab miR-200c) tau nce ntxiv thaum lub sijhawm raug mob thaum ntxov, thiab kev qhia ntawm lawv lub hom phiaj mRNAs tau cuam tshuam loj heev hauv lub raum medulla . Thaum lub sijhawm rov qab los thaum ntxov, exo-miRNAs uas sib koom Zeb1/2 raws li lub hom phiaj tseem ceeb tau raug kho kom zoo, hais txog lawv lub luag haujlwm hauv kev hloov pauv kev loj hlob (TGF)- 1- cuam tshuam rau lub raum fibrosis. Hauv ischemia-reperfusion raug mob, kev puas tsuaj hypoxic ua rau muaj kev tsim tawm ntawm EVs hauv tubular epithelial hlwb uas muaj TGF- 1 mRNA. Exosomal xa tawm ntawm cov TGF- 1 mRNAs mus rau hauv fibroblasts thaum kawg ua rau fibroblast ua kom thiab kev loj hlob. Ntawm qhov tod tes, Ranghino et al. Tsis ntev los no tau pom tias MSCs nyob rau hauv lub glomeruli tuaj yeem pab txhawb rau lub raum rov qab los ntawm kev tso tawm EVs.
Hauv sepsis-hais txog AKI, platelet-derived thiab neutrophil-derived EVs qhia txog cov teebmeem proinflammatory thiab procoagulant, uas tuaj yeem tiv thaiv kev loj hlob ntawm cov kab mob thiab nws cov kev nthuav tawm. Txawm li cas los xij, cov EVs no tuaj yeem ua rau muaj kev ntxhov siab oxidative thiab nthuav tawm cov lus teb, ua rau cov txiaj ntsig tsis zoo.
Tubulointerstitial o
Tubulointerstitial o yog ib yam ntxwv ntawm ob qho tib si mob thiabmob raum mob.Lv et al.pound ib qho kev nce ntxiv hauv tubular epithelial cell-derived exosomal miRNA-19b-3p hauv ob qho tib si lipopolysaccharide-induced AKI qauv thiab adriamycin-induced chronicproteinuric raumtus qauv kab mob. Tubular epithelial cell-derived exosomal miRNA-19b-3p txhawb M1 macrophage activation thiab tubulointerstitial o. Cov pab pawg no kuj tau pom tias exosomal xa ntawm CCL2 mRNA los ntawm tubular epithelial hlwb mus rau macrophages tuaj yeem kho albumin-induced tubulointerstitial o. Hypoxia yog lwm tus paub zoo stimulator ntawm tubulointerstitial o hauv lub raum. Hypoxic stimulation induces kev qhia ntawm hypoxia-inducible yam -1 nyob rau hauv tubular epithelial hlwb. Qhov kev txhawb nqa no ua rau exosomal miRNA-23 hloov pauv los ntawm tubular epithelial hlwb mus rau macrophages, uas ua rau macrophage activation thiab txhawb nqa tubulointerstitial o. Yog li, kev hloov pauv ntawm macrophage activation los ntawm kev thaiv exosomal miRNA lossis mRNA xa los ntawm tubular epithelial hlwb tuaj yeem yog txoj hauv kev kho tshiab.
Fibrosis
Fibrosis nyob rau hauv glomeruli thiab tubules yog qhov kawg pathologic txheej txheem ntawmmob raum mobthiab kawg-theemmob raum, thiab lub luag haujlwm pathophysiological ntawm EVs hauv fibrosis tau tshawb pom hauv ntau qhov kev tshawb fawb. Ntau yam stimuli ntawm lub raum hlwb, xws li hypoxia, oxidative kev nyuaj siab, los yog siab qabzib, tuaj yeem ua rau EV secretion lossis hloov pauv hauv EV muaj pes tsawg leeg. EVs secreted los ntawm lub raum puas hlwb yuav kis tau mus rau lwm lub raum lub cev, hloov lawv phenotype thiab activating fibroblasts. Nyob rau hauv cov xwm txheej hypoxic, puas hlwb epithelial hlwb hloov TGF- 1 mRNA mus rau fibroblasts los ntawm exosome secretion, thaum kawg ua rau proliferation / activation ntawm fibroblasts thiab kev loj hlob ntawm lub raum tubular fibrosis. Kev kawm hauv vitro los ntawm Wu et al. qhia tau hais tias EVs secreted los ntawm cov kua qab zib siab kho glomerular endothelial hlwb tuaj yeem ua rau podocyte epithelial-mesenchymal hloov pauv los ntawm kev hloov TGF- 1 mRNA rau hauv glomerular mesangial hlwb. Cov txheej txheem no ua rau cov cellular proliferation thiab overproduction ntawm extracellular matrix nyob rau hauv glomeruli, uas yog ib tug tseem ceeb pathological mechanism ntawm ntshav qab zib nephropathy. Ob peb miRNAs hauv EVs, xws li miR-21, miR-192, thiab miR-34a, kuj cuam tshuam rau cov txheej txheem lom neeg ntawm tubular fibrosis thiab glomerular fibrosis, feem.
Nephrolithiasis
Muab lub luag haujlwm tseem ceeb ntawm EVs ua tus neeg nruab nrab ntawm ntau yamkab mob raum, ntau qhov kev tshawb fawb tau kwv yees tias EVs muaj lub luag haujlwm hauv kev tsim pob zeb. Piv txwv li, ib qho kev tshawb fawb hauv vitro los ntawm He et al. qhia tau hais tias qhov tshwm sim ntawm lub raum tubular hlwb rau ntau qhov sib txawv ntawm oxalates tuaj yeem cuam tshuam qhov loj thiab muaj pes tsawg leeg ntawm exosomes los ntawm tubular hlwb. Qhov txiaj ntsig no qhia tau tias lub luag haujlwm lom neeg ntawm exosomes tuaj yeem nyob ntawm qib ntawm oxalate raug rau hauv microenvironment. Lwm yam kev tshawb fawb hauv vitro los ntawm Singhto et al. qhia tau hais tias exosomes muab tau los ntawm tib neeg macrophages raug rau calcium oxalate crystals tuaj yeem ua rau kev tsiv teb tsaws / ua kom cov monocytes / T-cell / neutrophils thiab txhim kho kev tsim cov proinflammatory cytokine interleukin -8. Cov exosomes no muaj peev xwm ntau dua los khi calcium oxalate crystals thiab tom qab ntawd txhim kho crystal ntxeem tau los ntawm extracellular matrix, qhia txog lub luag haujlwm ntawm macrophage-derived exosomes nyob rau hauv lub siv lead ua ntxeem tau ntawm lub raum interstitium.
Lub raum mob cancer
EVs kho cov kev sib txuas lus intercellular ntawm cov qog hlwb. EVs los ntawm cov qog nqaij hlav cancer muaj proangiogenic mRNAs thiab ntau yam miRNAs nrog cov qog-invasive zog. Clear renal cell carcinoma-derived EVs tuaj yeem cuam tshuam tsis zoo rau lub cev tiv thaiv kab mob los ntawm kev ua kom lub cev ntawm TGF- / SMAD signaling pathway. EVs kuj tseem paub txog kev kho mob chemoresistance nyob rau hauv lub raum mob qog noj ntshav los ntawm kev xa mus ntev noncoding / sib tw endogenous RNA, thaum kawg ua rau muaj kev qhia ntau dua ntawm prometastatic receptors. Cov ntaub ntawv ntxiv txog lub luag haujlwm ntawm EVs hauv urological malignancies tau piav qhia zoo hauv tsab xov xwm tshuaj xyuas los ntawm Linxweiler thiab Junker.
Extracellular vesicles ua biomarkers nyob rau hauv ntau yam kab mob raum
Feem ntau ntawm cov kev tshawb fawb EV hauv cov kab mob hauv lub raum tau tsom mus rau kev tshawb pom biomarker. EVs tuaj yeem pom muaj nyob rau hauv ntau hom tshuaj lom neeg xws li ntshav, zis, mis, kua cerebrospinal, qaub ncaug, ascites, thiab bronchoalveolar lavage kua. Raws li lub cev muaj zog, yuav luag tag nrho cov zis EVs tshwm sim los ntawm lub raum hlwb vim hais tias EVs feem ntau tsis mus rau hauv glomerular hauv qab daim nyias nyias. Yog li ntawd, lub hauv paus ntsiab lus tshwj xeeb ntawm cov zis EVs suav nrog qhov zoo ntawm kev siv cov zis EVs ua biomarkers hauvkab mob raum. Tsis tas li ntawd, EVs tso zis tuaj yeem tau txais tsis muaj kev cuam tshuam thiab rov ua dua, muab cov ntaub ntawv tseem ceeb hais txog kev kuaj mob, kev kuaj mob, thiab kev teb rau kev kho mob.
Txawm hais tias kev siv EVs tuaj yeem tshwm sim los ntawm cov kab mob sib txawv, ntshav ntshav, thiab ntshav ntshav, lawv tseem tuaj yeem muab cov ntaub ntawv tseem ceeb txog qhov twg thiab qhov tshwm sim ntawmmob raumvim tias qhov txiaj ntsig kev kho mob tau txiav txim siab tsis yog los ntawm lub raum kev puas tsuaj rau nws tus kheej nkaus xwb tab sis kuj los ntawm kev ua haujlwm tsis zoo ntawm cov khoom nruab nrog cev nrog rau lub ntsws, lub plawv, lub hlwb, lub siab, thiab lub cev tiv thaiv kab mob. Kev nkag tau yooj yim ntawm kev kho mob kuj tseem yog ib qho txiaj ntsig zoo ntawm kev siv cov EVs uas yog biomarkers hauv cov kab mob raum.
Kev nce qib tsis ntev los no hauv 'omic' cov kev tshawb fawb tau nthuav tawm qhov kev tshawb pom tshiab ntawm EV biomarkers ua kom pom cov txheej txheem pathologic txawm tias ntxov dua li cov tshuaj biomarkers. Salih et al.compared urinary EVs los ntawmautosomal dominant polycystic raum kab mob (ADPKD)cov neeg mob thiab kev noj qab haus huv tswj kev siv ntau yam proteomics. Ntawm cov proteins uas muaj ntau dua, tsib cov proteins suav nrog cov khoom ntxiv thiab cov platins raug xaiv rau kev tshuaj xyuas ntxiv raws li lawv qhov tseem ceeb hauv kev txheeb xyuas txoj hauv kev. Tshwj xeeb tshaj yog, qib siab dua ntawm kev ntxiv hauv cov zis EVs tau pom nyob rau hauv cov neeg mob ADPKD hluas nrog rau lub raum tsis ua haujlwm, tsa nws lub peev xwm ua biomarker. Vim muaj ntau cov ntaub ntawv los ntawm ntau yam kev tshawb fawb thiab qhov chaw tsawg, lub luag haujlwm ntawm EVs raws li biomarkers tau sau tseg hauv Table 2.
ADPKD, autosomal dominant polycystic raum kab mob; AGS3, tus activator ntawm G-protein signaling 3; AKI, mob raum raug mob; ATF3, activating transcription factor 3; CKD, mob raum mob; DN, ntshav qab zib nephropathy; DM, ntshav qab zib mellitus; EV, extracellular vesicle; FSGS, focal segmental glomerulosclerosis; IgA, immunoglobulin A; LN, lupus nephritis; lncRNA, ntev noncoding RNA; MCD, tus kab mob hloov tsawg heev; miRNA thiab miR, microRNA; mRNA, tub txib RNA; NGAL, neutrophil gelatinase-associated lipocalin; PKD, kab mob polycystic raum; RCC, lub raum cell carcinoma; RT-qPCR, rov qab transcription-quantitative polymerase saw cov tshuaj tiv thaiv; RT-PCR, rov qab transcription-polymerase saw cov tshuaj tiv thaiv; SH2D1B, SH2 domain-muaj protein ntau 1B; TIMP, cov ntaub so ntswg inhibitor ntawm metalloproteinase; TNF-, qog necrosis factor alpha; WT-1, Wilms qog 1.
Extracellular vesicles raws li kev kho mob nyob rau hauv ntau yam kab mob raum
Extracellular vesicles raws li kev thauj khoom ntawm cov khoom siv kho mob Lub luag haujlwm ntawm EVs raws li cov neeg nqa khoom tau txais kev saib xyuas tsis ntev los no. EVs muaj ntau yam txiaj ntsig zoo li vector tshaj lwm txoj hauv kev, suav nrog kev ruaj ntseg, me me, thiab kev tiv thaiv kab mob tsawg. Cov xovtooj ntawm tes tshwj xeeb ntawm cov molecules ntawm EVs nce lawv lub peev xwm nrog tsawg dua cov teebmeem. Nanosized EVs nrog qee qhov chaw molecules tuaj yeem nkag mus rau tej yam ntuj tso teeb meem xws li ntshav-hlwb barrier. Tsis tas li ntawd, EVs siv cov txheej txheem ib txwm muaj ntawm cov neeg tau txais cov hlwb nyob rau hauv chav kawm ntawm internalization thiab intracellular trafficking. Kev xa khoom ntawm biomolecular cargo xws li mRNA, miRNA, thiab cov proteins tuaj yeem hloov kho cov caj ces thiab cov lus teb lom neeg ntawm cov neeg tau txais cov hlwb, ua rau kev hloov pauv ntawm cov txheej txheem kab mob.
EV thauj khoom ntawm cov tshuaj ib txwm muaj los tiv thaiv cov khoom siv tau raug kawm rau kev siv tshuaj kho mob. Piv txwv li, Dexamethasone yog dav siv los txo qhov mob ntawm ntau yamkab mob raum, tab sis nws txoj kev siv tshuaj kho mob tsuas yog txwv vim muaj kev cuam tshuam loj heev. Los ntawm incubating macrophages nrog dexamethasone, macrophage-derived dexamethasone uas muaj EVs tau ntse tsim thiab xa mus rau lub raum mob ntawm nas, uas pom tau hais tias tseem ceeb tsub kom lub raum mob thiab fibrosis. Qhov tseem ceeb, dexamethasone uas muaj EVs tau txo qis qhov tsis zoo ntawm kev kho mob steroid xws li hyperglycemia thiab kev tawm tsam ntawm hypothalamic-pituitary-adrenal axis.
Hauv kaum xyoo dhau los, tau muaj kev nce qib hauv kev tshawb fawb EV. Interdisciplinary kev koom tes ntawm cov tshuaj thiab biomedical engineering tau siv EVs ua cov cuab yeej siv tshuaj muaj zog los ntawm kev siv nanotechnology. Ntau qhov kev tshawb fawb tau ua tiav cov khoom siv noob caj noob ces rau hauv EVs thiab pom muaj txiaj ntsig ntawm kev hloov kho kab mob. Yim et al. tsis ntev los no tau tsim cov txheej txheem tshiab rau kev hloov pauv hauv lub cev ntawm cov protein uas muaj kuab lom los ntawm exosomes los ntawm kev siv optogenetic engineering. Cov thev naus laus zis no tau txais kev pom zoo hauv kev sim sepsis qauv, qhia txog kev tiv thaiv ntawm exosomal super-repressor inhibitor ntawm kappa B (IκB) xa hauv murine septic AKI qauv. Tsis ntev los no, peb pab pawg kuj tau pom cov txiaj ntsig zoo ntawm exosomal super-repressor IκB xa hauv tus qauv ischemic AKI (hauv kev tshuaj xyuas).
Extracellular vesicles rau kho raum
Stem cell therapy muaj txiaj ntsig zoo hauv ntau qhov kev simmob raumcov qauv, tsis yog los ntawm lawv cov peev txheej sib txawv tab sis los ntawm cov teebmeem paracrine ntawm lawv cov EVs. EVs secreted los ntawm MSCs lossis endothelial progenitor hlwb tau pom tias ua lub luag haujlwm tseem ceeb hauv kev kho cov tubular cell apoptosis / fibrosis thiab proliferation ntawm tubular thiab endothelial hlwb nyob rau hauv ntau yam AKI qauv. Cov txiaj ntsig zoo no kuj pom muaj nyob rau hauv cov qauv kev sim kab mob raum ntev, ua kom muaj kev hloov pauv ntawm epithelial-rau-mesenchymal thiab tiv thaiv cov kab mob ntawm tes infiltration. MSCs uas tau tsim los rau overexpress miRNA-let7c tuaj yeem xaiv xa miRNA-let7c raulub raum puashlwb siv exosomes, uas coj mus rau kev tiv thaiv los ntawm lub raum raug mob thiab txo fibrosis nyob rau hauv ib tug unilateral ureteral obstruction qauv. Nagaishi thiab al.pom qhia tias MSC-los ntawm lub raum trophic yam xws li exosomes tuaj yeem txo qis albuminuria thiab tiv thaiv kab mob hauv lub raum hauv cov qauv ntshav qab zib nephropathy. MSC-derived exosomes pom cov nyhuv antiapoptotic thiab tiv thaiv nruj hlws ris qauv hauv tubular epithelial hlwb. Kev txhaj tshuaj ntawm cov urinary qia cell-derived exosomes kuj tseem tuaj yeem txo cov zis microalbumin excretion thiab tiv thaiv podocyte / tubular epithelial cell apoptosis hauv cov nas mob ntshav qab zib.
Sib nrug los ntawm MSCs, EVs los ntawm lwm lub hauv paus chiv keeb tau pom tias muaj kev tiv thaiv zoo rau tsiajmob raumqauv. Exosomes muab tau los ntawm sera ntawm cov tsiaj tom qab tej thaj chaw deb ischemic preconditioning tuaj yeem txo qis kev puas tsuaj rau lub raum, thiab qhov no tau kho los ntawm kev tswj hwm ntawm exosomal miRNA-21. Dominguez et al.pom qhia tias kev xa tawm ntawm EVs los ntawm cov nas lub raum tubular hlwb tuaj yeem txo cov raum puas hauv cov neeg tau txais kev pab tom qab ischemic insult. Cov pab pawg no kuj tau qhia tias tib neeg lub raum exosomes tuaj yeem tiv thaiv ischemic raum raug mob hauv cov nas liab qab. Txawm li cas los xij, cov pov thawj kho mob ntawm cov nyhuv renoprotective ntawm EV kev kho mob hauv tib neeg yog qhov tsawg. Ntau qhov teeb meem txwv kev siv tshuaj kho mob EVs hauv tib neeg; qhov tsis tshua muaj txiaj ntsig ntawm EVs los ntawm cov kab lis kev cai thiab kev sib cais EV ntxov ntxov / purification nrog kev pheej hmoo ntawm kev kis kab mob los ntawm lwm cov molecules uas muaj qhov sib xws. Txawm hais tias ntau qhov kev tshawb fawb tau pom tias muaj kev vam meej hauv EV kev rho tawm thiab ua kom huv huv, uas tau tshuaj xyuas lwm qhov, yuav tsum tau siv zog ntxiv los txhim kho kev sib cais thiab kev huv. Tsis tas li ntawd, kev tsim khoom loj yuav tsum tau siv rau kev kho mob ntawm EVs hauv tib neeg. Yang et al. Tsis ntev los no tau siv txoj kev cellular nano-poration los tsim cov exosomes loj uas muaj cov tshuaj mRNAs thiab tsom peptides. Los ntawm kev siv lub tswv yim no, lawv tuaj yeem tsim cov exosomes ntau dua thiab exosomal mRNA cov ntaub ntawv pov thawj piv nrog cov khoom siv hluav taws xob ntau thiab lwm cov tswv yim tsim tawm exosome. Thaum kawg, cov txheej txheem qib siab hauv kev hloov kho zoo ntawm EV cov ntsiab lus siv kev hloov pauv lossis kev tsim hluav taws xob ntawm tes yuav tsum tau xa cov ntawv teev lus tshwj xeeb lossis cov protein muaj pes tsawg leeg rau hauv lub hom phiaj. Qhov no yuav ua rau kom nkag siab zoo txog lub luag haujlwm lom neeg ntawm qee yam EVs hauv qhov tshwj xeebmob raumcov qauv thiab yuav nthuav dav cov kev siv kho mob ntawm EVs hauv ntau yamkab mob raum.
Extracellular vesicles raws li lub hom phiaj kho mob
Raws li peb tau hais, EVs tuaj yeem kho qhov kev nthuav tawm ntawm lub raum puas hauv cov kab mob septic, inflammatory, lossis thrombogenic mob. Yog li ntawd, ib ntus thaiv kev tso tawm thiab nce ntawm EVs tuaj yeem txo cov ntaub so ntswg puas. Ntau yam tshuaj siv tshuaj suav nrog cov tshuaj tiv thaiv kab mob, statins, calcium channel blockers, thiab abciximab tau pom tias muaj kev cuam tshuam tsis zoo rau cov txheej txheem ntawm EV tso tawm thiab nce ntxiv, uas tau tshuaj xyuas lwm qhov. Txawm li cas los xij, txawm tias thaiv qhov kev tso tawm thiab kev tso tawm ntawm EVs tuaj yeem cuam tshuam ncaj qha rau cov kab mob no tsis tau tshawb xyuas tag nrho. Kev tshawb fawb los ntawm Mossberg et al. qhia tau tias C1-inhibitor tuaj yeem txo qhov tso tawm ntawm chemotactic kinin B1-receptor-positive endothelial microvesicles, qhia tias nws muaj peev xwm kho tau cov kab mob inflammatory. Cov kev tshawb fawb ntxiv yuav tsum tau nkag siab txog kev siv tshuaj kho mob ntawm kev tswj EV kev cuam tshuam nrog cov neeg tau txais cov hlwb hauv cov kab mob inflammatory.
Cov lus xaus thiab kev pom
EVs koom nrog hauv kev sib txuas lus ntawm tes-rau-cell hauvlub raum,mediating podocyte-tubulointerstitial/proximal-distal tubular/glomerulus-tubular crosstalk. EVs tuaj yeem muab lub luag haujlwm physiological hauv kev kho lub raum thiab kev tiv thaiv kab mob los yog kho cov txheej txheem pathological uas ua rau thrombosis thiab mob. Cov kev tshawb fawb tsis ntev los no tau txhim kho peb txoj kev nkag siab ntawm lub luag haujlwm ntawm EVs hauvraumphysiology thiab pathology. Txawm li cas los xij, feem ntau ntawm cov txiaj ntsig tau txwv rau kev piav qhia transcriptomic / proteomic tsom xam thiab tsis muaj qhov sib xws nrog rau kev ntseeg tau. Kev siv zog nruj los ntawm kev sim tshuaj thiab kev tshawb fawb loj loj yog tsim nyog ua ntej nkag mus rau hauv daim ntawv thov kho mob. Kev ua kom zoo ntxiv ntawm EV cov txheej txheem cais tawm thiab kev tswj xyuas nruj ntawm cov khoom siv caj ces lossis cov protein sib xyaw ntawm EVs kuj tseem tsim nyog rau kev saib xyuas. Cov kev siv zog no yuav txuas ntxiv peb txoj kev paub txog lub luag haujlwm ntawm EVs hauv kev txhim kho / kev loj hlob ntawm cov kab mob hauv lub raum thiab yuav nthuav dav cov kev siv tshuaj kho mob ntawm EVs raws li kev kuaj mob tshiab thiab kev kho mob ntawm lub raum.kab mob raum.
Kev tsis sib haum xeeb
Tae-Hyun Yoo yog Pawg Thawj Saib Xyuas Kev Tshawb Fawb Txog Kev Tshawb Fawb ntawm ILIAS Biologics Inc. thiab Tus Thawj Saib Xyuas Haujlwm ntawmKev tshawb nrhiav raumthiab Clinical Practice. Chulhee Choi yog tus tsim thiab koom nrog ILIAS Biologics Inc. Cov kws sau ntawv tsis muaj kev txaus siab ntxiv nyiaj txiag.
Nyiaj txiag
Txoj haujlwm no tau txais kev txhawb nqa los ntawm cov nyiaj pab los ntawm National Research Foundation of Kauslim (NRF-2017R1A2B4005720, NRF-2017R1A2B3002241, NRF-2018M3A9E2022820, NRF-2019R1A2C2084535), uas yog nyiaj txiag). los ntawm tsoom fwv Kauslim (MSIP).
Kev lees paub
Cov kws sau ntawv kuj ua tsaug rau Kev Kho Mob Illustration & Tsim, ib feem ntawm Kev Pabcuam Kev Tshawb Fawb Txog Kev Kho Mob ntawm Yonsei University College of Medicine, rau txhua qhov kev txhawb nqa kos duab ntsig txog txoj haujlwm no.
Cov ntaub ntawv
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