Tshooj Ⅱ Lub luag haujlwm ntawm Mitochondrial DNA Kev puas tsuaj hauv cov kab mob raum: Ib Tug Biomarker Tshiab
Jun 13, 2023
mtDNA Kev faib tawm hauv cov kab mob raum
Feem ntau, tsis zoo mtDNA muaj nyob rau hauv mitochondrial matrix tab sis tsis nyob rau hauv cellular matrix, peripheral ntshav, los yog zis. Txawm li cas los xij, mitochondrial kev puas tsuaj ua rau muaj kev raug mob ntawm tes hauv ntau yam kab mob thiab feem ntau ua raws li mtDNA to los ntawm mitochondria thaum leaked mtDNA tsis txaus los ntxuav los ntawm kev kho cellular thiab phagocytosis system, lawv tuaj yeem raug tso tawm mus rau hauv peripheral ncig. mtDNA nyob rau hauv lub peripheral ncig filtrates los ntawm glomerular filtration barrier thiab koom nyob rau hauv tsim cov zis. Cell detachment nyob rau hauv lub urinary system, xws li lub zais zis thiab ureter, kuj tuaj yeem ua rau muaj mtDNA hauv cov zis. Yog li, mtDNA tuaj yeem kuaj pom hauv ob qho tib si peripheral plasma thiab zis. Cov theem ntawm mtDNA nyob rau hauv peripheral ntshav thiab zis tuaj yeem siv los ntsuas kev ua haujlwm mitochondrial thiab cov xwm txheej ntawm qee lub cev. Kuj tseem muaj ntau qhov kev tshawb fawb txog kev sib raug zoo ntawm mtDNA kev faib tawm thiab lub raum ua haujlwm (Daim duab 3).
Daim duab 3. mtDNA kev faib tawm hauv cov kab mob raum. mtDNA tuaj yeem kuaj pom nyob rau hauv ob qho tib si peripheral plasma thiab tso zis ntawm ntau lub raum kab mob xws li AKI thiab CKD. (AKI, mob raum raug mob; CKD, mob raum mob; IgA, Immunoglobulin A).
1. mtDNA hauv Peripheral Serum
Cov theem ntawm mtDNA nyob rau hauv peripheral serum yog kuj qis nyob rau hauv ib txwm physiological tej yam kev mob, thiab nws cov concentration yog nce nrog kev puas tsuaj rau ob peb lub cev los yog cov ntaub so ntswg, xws li raum, plawv, siab, hlwb, thiab nqaij [55-58]. Kev sib raug zoo ntawm plasma mtDNA thiab kab mob raum, suav nrog AKI thiab CKD, tau tshaj tawm. Tsis tas li ntawd, plasma mtDNA tau raug suav hais tias yog ib qho kev ntsuas rau kev ntsuas lub raum raug mob
Ntau yam tuaj yeem ua rau muaj qhov tshwm sim ntawm AKI, suav nrog ob sab ureteral obstruction, sepsis-associated AKI, glycerol-induced AKI, ischemia-reperfusion raug mob (IRI), thiab ob sab nephrectomy [59]. Kev kwv yees lub luag haujlwm ntawm plasma mtDNA hauv AKI tau raug coj los xav. Piv txwv li, qib plasma mtDNA tau nce hauv AKI cov neeg mob sepsis [60]. Hauv glycerol-induced AKI nas, qhov concentration ntawm plasma mtDNA tau nce tom qab 3 teev, qhia tias plasma mtDNA tuaj yeem yog qhov ntxov thiab rhiab biomarker ntawm AKI [61].
Ib txoj kev tshawb fawb tom qab hauv cov neeg mob lub raum tsis txaus ntseeg tau tshaj tawm tias qis dua mtDNA tus lej luam tau cuam tshuam nrog kev pheej hmoo siab dua ntawm CKD kev loj hlob, tsis muaj kev pheej hmoo tsim nyob rau hauv cov neeg mob CKD [62]. mtDNA tso tawm hauv platelets uas tau tsav los ntawm ib qho receptor rau lub cev tiv thaiv kab mob Fc RIIA yog qhov tseem ceeb ntawm mitochondrial antigens hauv cov kab mob lupus erythematosus [7]. Los ntawm kev tso cov mtDNA ntau dhau mus rau hauv kev ncig ntawm nas, qib siab ntawm cov ntshav mtDNA tuaj yeem ua rau mob thiab ua rau lub raum puas [63]. Plasma mtDNA yog ib qho kev kwv yees muaj zog ntawm cov xwm txheej hauv plawv nrog rau kev xav tau kev mus pw hauv tsev kho mob hauv cov neeg mob nrog peritoneal dialysis [64]. Hauv cov neeg mob uas tab tom kho hemodialysis (MHD), circulating mtDNA cov ntsiab lus tau nce siab dua hauv cov neeg mob sarcopenia, nrog rau siab dua TLR9 thiab IL-6 qhia, uas pom tau tias mtDNA tuaj yeem koom nrog hauv pathogenesis ntawm MHD ntsig txog sarcopenia [65] . Raws li ib qho ntawm cov proteins uas tsis tseem ceeb encoded los ntawm mtDNA, ntshav ND6 tau nce hauv cov tshuaj tiv thaiv antineutrophil cytoplasmic antibody-associated vasculitis, thiab ND6 concentration tau cuam tshuam tsis zoo nrog feem pua ntawm ib txwm glomeruli hauv raum biopsies [66]. Cov kev tshawb fawb no tau qhia tias cov ntshav mtDNA cuam tshuam txog kev tiv thaiv kab mob thiab lub raum raug mob.
Nyem qhov no kom paubDab tsi yog Cistanche
Serum mtDNA-mediated immune rejection txiav txim qhov ua tau zoo ntawm kev hloov lub raum. Qhov siab dua qib ntawm cov ntshav mtDNA hauv lub raum pub dawb, qhov ntau dua rau tus neeg tau txais kev hloov pauv hauv lub raum yog muaj kev tsis lees paub cov tshuaj tiv thaiv kab mob. Yog li ntawd, tus neeg pub ntshav ntshav mtDNA tuaj yeem siv los ua tus cim kev kwv yees rau kev tsis lees paub cov tshuaj tiv thaiv kab mob thiab kev ntsuas tus neeg pub khoom noj muaj txiaj ntsig [67]. Yog li, tus neeg pub ntshav ntshav mtDNA yog ib qho kev pheej hmoo ntawm kev ywj pheej rau ncua sij hawm graft muaj nuj nqi (DGF) ntawm cov neeg tau txais lub raum, uas yog qhov tseem ceeb hauv kev ntsuam xyuas lub cev [68].
2. mtDNA hauv zis
mtDNA hauv cov zis tuaj yeem siv los ua qhov ntsuas los ntsuas lub raum ua haujlwm. Ib qho mob hnyav ntxiv hauv cov zis mtDNA los ntawm percutaneous transluminal raum angioplasty qhia txog lub raum mitochondrial puas thiab yog li inhibits lub raum rov qab [69]. Hauv cov neeg mob uas muaj tus kab mob sepsis, urinary mtDNA nce qib tau cuam tshuam nrog mitochondrial dysfunction thiab lub raum raug mob, qhia tias sepsis ua rau lub raum mitochondrial raug mob. Yog li ntawd, urinary mtDNA tej zaum yuav suav hais tias yog ib qho tseem ceeb biomarker rau kev txiav txim siab txoj kev loj hlob ntawm AKI thiab mitochondria-targeted therapy tom qab sepsis-induced AKI [70]. Piv nrog rau kev tswj hwm kev noj qab haus huv, kev qhia ntawm STING hauv lub raum tau nce ntxiv thiab qib mtDNA urinary tau nce siab hauv cov neeg mob hloov pauv tsawg (MCD), uas tuaj yeem siv los ua tus cim tseem ceeb hauv MCD [71]. Cov theem ntawm cov zis mtDNA tau nce siab hauv cov neeg mob ntshav qab zib thiab cov nas, uas tsis zoo cuam tshuam nrog glomerular filtration rate thiab muaj kev cuam tshuam zoo nrog interstitial fibrosis [63,72]. mtDNA kuj tau yooj yim kuaj pom nyob rau hauv cov zis supernatant ntawm nondiabetic CKD thiab nws qib sib cuam tshuam nrog tus nqi ntawm lub raum tsis ua haujlwm thiab kwv yees qhov kev pheej hmoo ntawm cov ntshav siab creatinine thiab xav tau kev lim ntshav hauv cov neeg mob CKD [73]. Cov zis qis mtDNA tau cuam tshuam nrog cov txiaj ntsig zoo rau lub raum ntawm 6 lub hlis tom qab, qhia txog lub luag haujlwm tshiab prognostic ntawm mtDNA rau lub raum tshwm sim hauv cov neeg mob CKD [74]. Hauv cov neeg mob renovascular hypertensive, nce urinary mtDNA tus lej luam tau cuam tshuam nrog mitochondrial dysfunction thiab lub raum raug mob, suav nrog nce urinary neutrophil gelatinase-associated lipocalin, raum raug mob molecular -1 (KIM-1) qib, thiab txo qis glomerular. pom [75,76]. Cov zis ntau dua mtDNA cov lej luam tawm thiab siab dua txhais tau tias txhua xyoo ntawm kwv yees glomerular filtration rate (eGFR) poob tau tshwm sim hauv cov neeg mob glomerular abnormalities thiab IgA nephropathy (IgAN), thiab kev raug mob mitochondrial tuaj yeem ua ntej kev hloov pauv pathological thiab nce proteinuria [77,78]. Urinary mtDNA tau nce siab hauv cov neeg mob antineutrophil cytoplasmic autoantibodies-associated vasculitis (ANCA-AAV) cov neeg mob uas muaj lub raum tsis ua haujlwm thiab nws qib cuam tshuam nrog rau qhov hnyav ntawm lub raum raug mob thiab pathological neutrophil infiltration [79]. Cov theem ntawm cov zis mtDNA tau cuam tshuam nrog lub sijhawm txias ischemia thiab lub raum ua haujlwm hauv tib neeg lub raum hloov pauv, uas cuam tshuam nrog rau lub raum allograft muaj nuj nqi thiab kev kuaj mob ntawm DGF tom qab hloov lub raum [80]. Cov zis mtDNA qib tau nce siab dua hauv cov neeg mob uas tsis kam lees thiab DGF, uas tuaj yeem kwv yees txog lub sijhawm luv luv tom qab hloov lub raum ua haujlwm [81]. Muab ua ke, cov kev tshawb fawb saum toj no qhia tau hais tias mtDNA hauv cov zis muaj feem cuam tshuam nrog kev hloov pauv hauv lub raum ua haujlwm hauv ntau hom kab mob raum thiab qib siab ntawm cov zis mtDNA yog qhov tsis zoo.
Cistanche tubulosa
mtDNA Kev puas tsuaj hauv raum kab mob
1. Impaired mtDNA Replication
mtDNA replicates hauv kab lis kev cai ntawm lub raum los ntawm asynchronous mechanism [82]. Kev txo qis mtDNA tus lej luam hauv cov qauv ntshav tau cuam tshuam nrog qib qis ntawm cov ntshav creatinine, uas qhia tias lub raum tsis ua haujlwm [83]. Thaum lub sij hawm mtDNA replication, lub luag hauj lwm ntawm mtSSB1 yog los tiv thaiv displaced ib leeg-stranded DNA los ntawm kev puas tsuaj, los tiv thaiv kev tsim ntawm DNA thib ob qauv, thiab kev khi tsis tsim nyog DNA synthesis thiab catabolic enzymes. Gustafson et al. tshaj tawm ib rooj plaub ntawm ib tug hluas CKD tus neeg mob harboring mtSSB1 kev hloov pauv (p.E27K) nrog rau ib qho loj-scale mtDNA tshem tawm [84]. mtDNA cov ntsiab lus ntawm lub raum kuj tseem txo qis hauv SSBP1 kev hloov pauv (p.R107Q) cov neeg mob uas pom OXPHOS tsis zoo thiab lub raum ua haujlwm tsis txaus yuav tsum tau hloov pauv [85]. Tsuas yog rau mtDNA ntawm lub hlwb, lub raum mtDNA yog qhov yooj yim tshaj plaws rau kev puas tsuaj rau lub hnub nyoog, thiab cov ntawv luam ntawm mtDNA hauv ob lub raum ntawm cov nas hnub nyoog tau nce ntau [86]. Tsis tas li ntawd, mtDNA qib tau nce siab dua nyob rau hauv cov tubules ze ze thiab cov distal ntau dua li hauv glomerular thiab khaws cov duct epithelium ntawm lub raum. Nrog rau lub hnub nyoog nce, mtDNA cov ntsiab lus tau txo qis hauv lub raum tubules, uas zoo ib yam nrog rau lub raum ua haujlwm tsis zoo thiab tuaj yeem thim rov qab los ntawm kev txwv caloric [87]. Zuag qhia tag nrho, mtDNA replication yog ib tug biomarker ntawm mitochondrial muaj nuj nqi, uas yog txuam nrog nce kev tuag thiab morbidity nyob rau hauv cov kab mob uas muaj hnub nyoog [88].
Cov kev tshawb fawb tsis ntev los no tau qhia tias qhov tsis zoo ntawm mtDNA replication ua rau AKI. mtDNA replication thiab cov ntsiab lus tau txo qis nrog kev txhim kho mitophagy hauv lub raum, uas ua rau muaj qhov tshwm sim ntawm AKI thiab nce kev tuag ntawm cov nas hloov siab [89]. mtDNA tus lej luam tau txo qis hauv lub raum fibrosis qauv, suav nrog unilateral ureteral obstruction (UUO) thiab IRI, nrog rau mitochondrial dysfunction thiab oxidative stress [90]. Hypoxia-inducible factor-1 (HIF-1 )-BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)-mediated mitophagy regulated mtDNA the copy number and ROS production and inhibited cell apoptosis in renal tubular cells ntawm IRI qauv [91].
Ntau yam ua rau CKD muaj nyob nrog qhov txawv txav mtDNA replication. Qhov txo qis mtDNA tus lej luam nyob rau hauv peripheral ntshav mononuclear hlwb ntawm MHD cov neeg mob tau kwv yees cov txiaj ntsig kev kho mob tsis zoo [92]. Raws li qhov tshwm sim, mtDNA tus lej luam tau txo qis hauv lub raum ntawm cov nas mob ntshav qab zib, nrog rau kev txo qis TFAM qhia thiab ATP ntau lawm [93]. Ib yam li ntawd, peb txoj kev tshawb fawb yav dhau los tau pom tias qhov cuam tshuam ntawm mtDNA replication nyob rau hauv podocytes pab rau lub raum raug mob nyob rau hauv cov ntshav qab zib raum kab mob (DKD) [94]. mtDNA deletion kuj aggravated podocyte raug mob thiab depletion, uas yog koom nyob rau hauv lub pathogenesis ntawm focal segmental glomerulosclerosis (FSGS) [95]. Kev txo qis hauv mtDNA cov ntsiab lus yog qhov ua rau txo qis OXPHOS hauv chromophobe raum mob cancer (ChRCC) [96]. Txoj kev tshawb fawb tshiab no tau pom tias mtDNA replication defects coj mus rau tsim mtDNA linear deletion, uas ua rau lub cev tsis muaj zog thiab ua rau muaj mob raum rau cov tsiaj laus [97].
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2. mtDNA Kev hloov pauv
Lub raum tsis yog ib qho khoom nruab nrog siab mtDNA replication. Nws kuj muaj ntau qhov chaw hloov pauv mtDNA uas tuaj yeem hloov pauv [98]. Cov nyhuv downstream ntawm mtDNA kev hloov pauv yog mitochondrial dysfunction. mtDNA kev hloov pauv feem ntau ua rau cov kab mob hauv lub cev, uas tseem tuaj yeem cuam tshuam nrog kev loj hlob ntawm AKI thiab CKD [28]. Cov kab mob hauv lub raum tshwm sim los ntawm mtDNA kev hloov pauv ntawm qhov chaw sib txawv tau sau tseg hauv Table 1.
An adenine to guanine substitution at nucleotide 3243 of the mtDNA (m.3243A>G), which affects the mitochondrial MT-TL1 gene, has been shown to cause mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The most striking characteristics of renal biopsy were FSGS and arteriolar hyaline thickening [116]. Cai et al. recently reported that a patient with m.3243A>G kev hloov pauv tau kuaj pom muaj membranous nephropathy, thiab AKI nyuaj los ntawm hyperuricemia yuav raug ntaus nqi rau mtDNA kev hloov pauv [99].
A novel heteroplasmic nonsense mtDNA mutation m.6145G>A in the mitochondrial cytochrome c oxidase subunit I (MTCO1) was also identified in a patient who exhibited mitochondrial abnormalities, chronic tubulointerstitial changes and recurrent episodes of rhabdomyolysis [100]. Mitochondrial tubulointerstitial nephropathy (MITKD) is a tubulointerstitial nephropathy caused by mutations in mtDNA. m.616T>C is one of the mutations that lead to MITKD, the main symptoms of which are chronic renal insufficiency and Epilepsia [101]. It has also been reported that two mt-ND5 pathogenic variants m.13513G>A and m.13514A>G caused mitochondrial dysfunction in tubulointerstitial kidney disease [102]. Aristolochic acid elevated the levels of mutagenic 8-oxo-20 -deoxyguanosine and 7-(deoxyadenosine-N6-yl)-aristo lactam adduct on mtDNA isolated from human HEK293 cells, which shed light on a potentially important causative role of mtDNA mutations and mitochondrial dysfunction in the etiology of aristolochic acid nephropathy [117]. Patients with type 2 diabetes diagnosed with the m.4216T>C mtDNA mutation are more likely to have poor glycemic control, which triggers the progression of DKD [103]. However, an mtDNA mutation m.8344A>G nyob rau hauv mitochondrial tRNALys noob ua rau myoclonic qaug dab peg nrog ragged-liab fibers (MERRF) syndrome tsis cuam tshuam mtDNA tus lej lej thiab lub raum ua haujlwm [118].
Kev ua tiav mtDNA rov ua dua tau siv rau kev kuaj xyuas kev hloov pauv hauv cov qauv kuaj mob thiab ntau hom qog nqaij hlav tau kuaj xyuas mtDNA kev hloov pauv, suav nrog rau lub raum cell carcinoma (RCC) [119]. Kev hloov pauv ntawm mtDNA pom kev hloov pauv hauv cov noob ntawm mitochondrial complex I subunit ND1, ND5, thiab ND6, uas ua rau muaj kev ua pa tsis txaus thiab qhov tshwm sim ntawm lub raum oncocytoma [104]. ChRCC yog ib qho subtype ntawm RCC, uas yog nrog los ntawm tus nqi siab ntawm mtDNA kev hloov pauv [120]. mtDNA sequencing tsom xam qhia tias mtDNA kev hloov pauv tau ua rau kev ua haujlwm tsis txaus ntawm NADH dehydrogenase subunits, uas ntxiv txhawb kev hloov pauv ntawm cov qauv metabolic hauv ChRCC [105].
Standardized Cistanche
3. mtDNA Leakage
Lub raum yog ib lub cev uas nplua nuj nyob hauv mtDNA. Thaum lub raum raug txhawb los ntawm cov teeb meem tsis zoo, mtDNA tuaj yeem tso tawm ntawm mitochondrial matrix mus rau cytoplasm. Cisplatin-induced mtDNA to mus rau hauv cytosol, tej zaum yuav los ntawm BAX pores nyob rau hauv lub mitochondrial txheej membrane nyob rau hauv lub raum tubules nrog rau tom qab ua kom cov cGAS-STING txoj kev, yog li ua rau o thiab AKI kev loj hlob [121]. Cov receptor-interacting protein kinase 3 hloov mus rau mitochondria thiab cuam tshuam nrog mitofilin, uas ua rau muaj zog mtDNA tso tawm thiab ua kom cov cGAS-STING-p65 txoj hauv kev raum IRI [122]. Hauv cov nas nrog tubule tshwj xeeb knockout ntawm TFAM, kev ntim khoom tsis zoo ntawm mtDNA ua rau cytosolic translocation, uas txuas ntxiv mus rau cytosolic cGAS-STING txoj hauv kev thiab nrhiav cytokine thiab lub cev tiv thaiv kab mob kom ua rau lub raum fibrosis [123]. Hauv DKD, kev txo qis ntawm superoxide dismutase 2 kho kom haum mitochondrial tsis ua haujlwm thiab mtDNA to, uas tuaj yeem qhib TLR9 hauv macrophages [124]. Hauv cov ntsiab lus, mtDNA to tuaj yeem yog qhov tshwm sim ntawm lub raum raug mob thiab kho qhov kev txhim kho ntawm ntau cov lus teb.
4. mtDNA Methylation
Cov kev tshawb fawb tam sim no ntawm mtDNA methylation hauv lub raum tseem yog qhov muag tsis pom. Tsuas yog ib qho kev tshawb fawb txog kev sib raug zoo ntawm lub raum qog metastasis thiab mtDNA methylation tau tshaj tawm. Nws tau pom tias, piv rau thawj RCC hlwb, thaj tsam D-loop ntawm mtDNA tau pom tias muaj hypermethylated hauv cov pob txha metastatic RCC hlwb, uas muab kev sib txuas ncaj qha ntawm hypermethylation ntawm mtDNA hauv RCC thiab cov qog loj hlob hauv cov pob txha metastases [125]. Vim muaj kev txwv kev siv thev naus laus zis thiab cov nqi nyuaj hauv kev tshawb nrhiav mtDNA methylation, txoj kev kawm hauv cheeb tsam no kuj tsis zoo. Nrog rau kev saib xyuas thiab kev mob siab rau kev tshawb nrhiav ntawm daim teb no, lub luag haujlwm ntawm mtDNA methylation hauv cov kab mob raum yuav raug tshawb nrhiav tsis tu ncua.
Cistanche ntxiv
Pharmacological Intervention ntawm mtDNA Kev puas tsuaj hauv raum kab mob
Raws li tau tham hauv nqe lus dhau los, cov ntsiab lus thiab kev ncaj ncees ntawm mtDNA hauv lub raum yog qhov tsis zoo hauv etiology ntawm ntau yam kab mob raum. mtDNA puas tuaj yeem cuam tshuam ncaj qha rau kev ua haujlwm mitochondrial. Yog li ntawd, cov phiaj xwm kev cuam tshuam tawm tsam mtDNA kev puas tsuaj yuav muaj kev kho mob rau cov kab mob raum.
Tam sim no muaj ntau yam tshuaj siv los cuam tshuam rau lub raum mtDNA kev puas tsuaj, raws li qhia hauv Table 2. Peb tau piav qhia txog cov tshuaj siv tshuaj ntawm cov neeg ua haujlwm no thiab pom tias feem ntau ntawm lawv txo cov mob raum thiab cellular apoptosis los ntawm kev txhim kho mitochondrial zog, xws li nce mtDNA. cov ntsiab lus, peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1 ), thiab peroxisome proliferator-activated receptor (PPAR) qhia, uas txhawb nqa mitochondrial OXPHOS los pab txhawb lub zog thiab txo oxidative kev nyuaj siab, ROS ntau lawm, thiab mob. Kuj tseem muaj ob peb tus neeg ua haujlwm kho mob, xws li l-carnitine thiab sacubitril / valsartan, uas ua rau txo qis cov lus teb inflammatory tau qhib los ntawm mtDNA leakage ntawm suppressing o-txog txoj kev, xws li TLR9 thiab cGAS-STING signaling pathways [124,126].
Ob peb lwm txoj kev kho mob kuj tau tshaj tawm. Piv txwv li, extracellular vesicles (EVs) muab tau los ntawm mesenchymal qia hlwb (MSCs) muaj cov khoom ua haujlwm mitochondrial, xws li mtDNA, mitochondrial proteins, thiab cov proteins uas muaj zog los ntawm lub voj voog tricarboxylic acid [135]. MSC-EV-mediated TFAM mRNA hloov kho TFAM qhia, mtDNA tshem tawm, thiab OXPHOS tsis xws luag hauv lub raum tubular hlwb ntawm AKI [136]. Cov kev tshawb fawb tshiab qhia tau hais tias kev hloov pauv mitochondrial tej zaum yuav yog kev kho tshiab rau cov kab mob mitochondrial. Direct exogenous supplementation ntawm mitochondria tuaj yeem hloov cov mtDNA puas, rov ua haujlwm mitochondrial, thiab inhibit oxidative kev nyuaj siab, yog li txo apoptosis [137,138]. Ntxiv mus, mitochondrial hloov kho tuaj yeem siv rau cov kab mob ntawm niam txiv los ntawm kev hloov pauv hauv mtDNA [139].
Cov lus xaus thiab cov kev xav yav tom ntej
Intact mtDNA yog ze ze rau kev ua haujlwm mitochondrial. mtDNA tsis muaj kev kho tus kheej zoo thiab muaj kev cuam tshuam rau ntau yam sab nraud thiab sab hauv, suav nrog tshuaj, kab mob, kev tiv thaiv kab mob, kub siab, ntshav qab zib, thiab kev laus. Tag nrho cov etiologies no tuaj yeem ua rau muaj kev puas tsuaj rau mtDNA, uas ntxiv dag zog rau mitochondrial dysfunction, manifested raws li tsis zoo ETC, txo OXPHOS, thiab oxidative kev nyuaj siab thiab inflammatory teb, yog li koom nyob rau hauv cov txheej txheem ntawm lub raum raug mob. Yog li ntawd, nws yog ib qho tseem ceeb los tshawb nrhiav lub luag haujlwm ntawm mtDNA kev puas tsuaj hauv lub raum kab mob.
Hauv kev tshuaj xyuas no, peb tau txheeb xyuas ntau hom kev puas tsuaj ntawm mtDNA, suav nrog kev cuam tshuam mtDNA replication, mtDNA hloov, mtDNA to, thiab mtDNA methylation. Cov txheej txheem ntawm cov hom kev puas tsuaj no tau piav qhia dav dav, thiab cov kev tshawb fawb ntsig txog mtDNA kev puas tsuaj hauv cov kab mob raum kuj tau piav qhia meej. Nws tau raug tshaj tawm tias kev puas tsuaj mtDNA ua lub luag haujlwm tseem ceeb hauv cov kab mob hauv lub raum thiab cov theem ntawm mtDNA hauv cov ntshav peripheral thiab cov zis tau qhia tias muaj lub luag haujlwm tseem ceeb hauv cov kab mob raum. Pharmacological kev kho mob lossis exogenous mtDNA hloov pauv tuaj yeem txhim kho mtDNA puas, rov ua haujlwm mitochondrial, lossis ncaj qha inhibit mtDNA-vim cov lus teb, yog li muab lub hauv paus theoretical thiab txoj hauv kev tshiab rau kev kho mob raum. Hauv kev xaus, mtDNA kev puas tsuaj yog ib qho tseem ceeb biomarker ntawm cov kab mob raum.
Cov ntaub ntawv
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Jun Feng 1,2, Zhaowei Chen 1,2, Wei Liang 1,2, Zhongping Wei 1,2 thiab Guohua Ding 1,2,
1 Division of Nephrology, Renmin Tsev Kho Mob ntawm Wuhan University, Wuhan 430060, Suav
2 Nephrology thiab Urology Research Institute ntawm Wuhan University, Wuhan 430060, Suav
