Ntu 2: Proteinuric Mob raum Kab Mob Sib Kis Nrog Hloov Cov Ntshav Liab Cell Lifespan, Deformability Thiab Metabolism

Rau Part 1, Thov niasNtawm no.

Hu rau: emily.li@wecistanche.com

Doxorubicin-induced raum raug mob hloov murine RBC lifespan, morphology, thiab biophysical zog

Nees nkaum hnub tom qab induction ntawm DIN, coinciding nrog kev loj hlob ntawm txolub raum ua haujlwm(Daim duab 1b), fluorescent dye 5(6)-CFDA, SE,24 uas tau coj mus rau hauv RBCs sai sai, tau iv txhaj tshuaj xyuas RBC clearance tus nqi ntawm lub sij hawm taw qhia hauv vivo. Cov neeg sawv cev histograms, pom hauv daim duab 4a, qhia txog kev tshem tawm cov ntawv sau npe RBCs los ntawm kev ncig thiab hloov los ntawm RBCs tsis muaj npe. Kev nce RBC poob tau pom meej 3 hnub tom qab kev tswj hwm cov xim, thiab kev tshem tawm ntawm RBCs tau nrawm dua hauv 129S1 / SvImJ nas nrog DIN mus txog hnub 37. Hnub 41, z17 feem pua ​​​​ntau RBCs raug tshem tawm ntawm kev ncig hauv cov nas piv rau. nrog nas noj qab nyob zoo (Daim duab 4b).

Cistanchetxhim kholub raum ua haujlwmthiabcov txiaj ntsiglub raum

Cov duab coj los ntawm cov ntshav smear tau qhia txog kev hloov pauv ntawm morphologic hauv RBCs kos los ntawm 129S1 / SvImJ nas nrog DIN (Daim duab 4c) thiab Nphs2Dipod nas (Ntxiv daim duab S4A). Nyob rau hauv cov nas noj qab haus huv, RBCs tso saib cov duab biconcave disc. Hauv 129S1 / SvImJ nas nrog DIN, peb tau pom ntau tus stomatocytes (cov hnub qub liab), teardrop cells (dub daim duab peb sab), schistocytes (dub cov ntsiab lus), thiab microcytic hlwb (dub xub) (Daim duab 4c). Nphs2Dipod nas pom qhov nce ntawm cov schistocytes (cov ntsiab lus dub, Cov duab ntxiv S4A, cov duab qis dua, sab laug), thiab cov hlwb tau polychromatic (Cov duab ntxiv S4A, cov duab qis dua, sab xis).

Txhawm rau tshawb xyuas ntxiv RBC kev hloov pauv, kev ntsuas deformability rau hnub 30 tau ua tiav siv ektacytometry.³²RBC deformability tau txo qis hauv 129S1 / SvImJ nas nrog DIN nrog rau hauv Nphs2Dipod nas, raws li qhia los ntawm qhov txo qis qhov siab tshaj plaws elongation Performance index (EImax) (Daim duab 4d thiab Cov Duab Ntxiv S4B). Shear stress rau 50 feem pua ​​(SS1/2) ntawm EImax (Daim duab 4e) thiab, yog li, SS1/2 EImax piv (Daim duab 4f) tau nce 129S1/SvImJ nas nrog DIN, qhia tias stiffer RBCs. SS1/2 ntawm EImax tau zoo sib xws hauv Nphs2Dipod nas (Ntxiv daim duab S4C). SS1/2 EImax ratio tended to be augmented in Nphs2Dipod nas piv nrog noj qab nyob zoo C57BL/6 nas; Qhov sib txawv tau, txawm li cas los xij, tsis ncav cuag qhov tseem ceeb (P ¼ 0.06) (Cov Duab Ntxiv S4D).

Raws li raug RBCs rau hypertonic extracellular tej yam kev mob nyob rau hauv vitro mimics lub osmotic ib puag ncig ntsib nyob rau hauv lub raum medulla, ib cosmos yuav ua tau nyob rau hnub 30 thiab ob peb osmosensitive tsis tau txiav txim, raws li tau piav yav tas los.³³ Omin sawv cev rau osmolality ntawm qhov tsawg kawg nkaus RBC deformability, dhau qhov uas RBCs yuav lyse nrog ib tug ntxiv txo nyob rau hauv osmolarity. Omin qhov tseem ceeb tau siab dua hauv 129S1 / SvImJ nas nrog DIN thiab hloov mus rau sab xis (Daim duab 5a thiab d). Ib qho kev xav zoo sib xws rau Omin siab dua tau pom hauv Nphs2Dipod nas (Ntxiv daim duab S4E). Cov txiaj ntsig ntawm Ohyper, cuam tshuam txog lub xeev dej ntawm cov hlwb, tau muaj txiaj ntsig ntau dua hauv 129S1 / SvImJ nas nrog DIN (Daim duab 5b) tab sis zoo ib yam hauv Nphs2Dipod nas thiab lawv cov nas tswj hwm (Cov duab ntxiv S4F). Qhov siab tshaj plaws deformability (EImax) ntawm isotonicity yog qhov taw tes ntawm cov hlwb tau txais qhov siab tshaj plaws ellipticity. EImax ntawm isotonicity tau txo qis hauv 129S1 / SvImJ nas nrog DIN (Daim duab 5c) tab sis tsis pom qhov sib txawv ntawm Nphs2Dipod nas piv nrog cov nas noj qab haus huv C57BL / 6 (Ntxiv daim duab S4G). Zuag qhia tag nrho, cov txiaj ntsig no qhia txog kev txo qis kev ntseeg siab thiab elasticity tab sis kuj hloov pauv hauv 129S1 / SvImJ thiab Nphs2Dipod nas nrog rau ntau dua osmotic fragility ntawm RBCs los ntawm 129S1 / SvImJ nas nrog DIN.

RBCs yog metabolically reprogrammed thaum muaj proteinuric raum kab mob hauv nas

Txhawm rau kom nkag siab zoo dua cov kev hloov pauv ntawm cov molecular cuam tshuam nrog cov kev hloov pauv hauv RBC abundance thiab morphology raws li kev ua haujlwm ntawm lub raum raug mob, RBCs los ntawm 129S1 / SvImJ nas nrog DIN thiab Nphs2Dipod nas tau txheeb xyuas los ntawm huab hwm coj spectrometry-based metabolomics (Daim duab 6a thiab Supplementary Figure S5A). Siv txoj hauv kev no, cov txheeb ze ntawm 256 metabolites tau txiav txim siab rau 129S1 / SvImJ nas thiab Nphs2Dipod nas. Txhawm rau txheeb xyuas cov ntaub ntawv no hauv cov txheej txheem, kev tshuaj xyuas ntau yam, suav nrog kev txheeb xyuas ib nrab-tsawg squares cais tawm thiab kev txheeb xyuas hierarchical pawg, tau ua. Interestingly, ib nrab-tsawg squares cais kev tsom xam ntawm RBC metabolomes los ntawm ob qho tib si qauv qhia cov qauv zoo sib xws.

Tshwj xeeb, txawm hais tias cov qauv ntawm lub sijhawm ntawm cov qauv induction pawg ua ke nrog cov qauv kev noj qab haus huv los ntawm txhua lub sijhawm cov ntsiab lus, cov qauv los ntawm cov nas nephrotic pawg tau sib cais ntawm nws tus kheej los ntawm cov qauv tswj kev noj qab haus huv nrog rau cov khoom 1 (Daim duab 6b thiab ntxiv daim duab S5B). Nyob rau hauv txoj kab nrog pawg qauv pom tseeb hauv 2 qauv, hierarchical clustering tsom xam ntawm cov ntaub ntawv metabolomics rau txhua tus qauv qhia txog cov qauv zoo sib xws rau cov metabolites koom nrog oxidative kev nyuaj siab, nrog rau nucleo-tides, amino acids, acylcarnitines, thiab fatty acids (Daim duab 6c. thiab Cov Duab Ntxiv S5C, S6, thiab S7). Piv txwv li, qib ntawm allantoin, purine catabolite thiab cov cim ntawm oxidative kev nyuaj siab hauv RBCs,³⁴ thiab txo glutathione ob qho tib si tseem ceeb tau sau ntau lub sij hawm hauv ob qho tib si nephrotic nas qauv, qhia txog kev tsim cov pa oxygen tsis tu ncua thiab ua kom muaj zog ntawm cov kab mob antioxidant glutathione (Daim duab 6d thiab ntxiv daim duab S5D). Ib yam li ntawd, cov qib ntawm coenzyme A (CoA) precursor pantothenate tau sau ntau lub sijhawm (Daim duab 6e thiab Cov Duab Ntxiv S5E).

Cov qauv zoo sib xws tau tshwm sim nyob rau hauv cov qib ntawm cov roj fatty acids dawb hexadecenoic acid (C16: 1), octadecenoic acid (C18: 1), thiab docosapentaenoic acid (C22: 5), txawm hais tias txhua tus qauv muaj cov qauv ntawm lub cev (Daim duab 6f thiab cov duab ntxiv. S5F).

Nyob rau sab saum toj ntawm fatty acids, acylcarnitines, nrog rau hydroxyoctanoyl-carnitine (AC C8-OH), hydroxydecanoyl-carnitine (AC C10-}OH), thiab dodecanoyl-carnitine (AC C12: 1), kuj teb. rau induction ntawm proteinuric nephropathy nyob rau hauv ob qho tib si qauv (Daim duab 6g thiab Supplementary Figure S5G).

Ua ke, cov kev tshawb pom no qhia tau hais tias ntawm induction ntawm proteinuricmob raumHauv 2 tus qauv nas zoo sib xws, nce qib ntawm oxidative kev nyuaj siab tuaj yeem cuam tshuam kev puas tsuaj rau acyl chains ntawm daim nyias nyias lipids. Vim tias RBCs tsis muaj peev xwm los tsim cov lipids tshiab, lawv siv cov txheej txheem uas nyob ntawm phospholipase-mediated tshem tawm cov acyl chains puas thiab hloov nrog cov roj fatty acids uas tsis muaj kev puas tsuaj. Kev xa mus rau lub voj voog av, 35 qhov system no nyob ntawm acyl-chain activation los ntawm kev sib txuas rau CoA, uas tsim kom muaj kev sib npaug nrog acylcarnitine rau daim nyias nyias hloov 36 (Daim duab 6h thiab Daim Duab Ntxiv S5H).

Proteinuric CKD cov neeg mob uas muaj ntshav liab tuaj yeem txhim kho RBC kev tuag

To confirm that PS-exposing RBCs occur also in human CKD, as described earlier,37 we analyzed blood samples from 25 patients treated by our outpatient clinic. To match the mouse models that represent nephrotic syndrome with preserved GFR during the first 10 days, and then advanced CKD with reduced GFR from day 20 onwards (Figure 1 and Supplementary Figure S2), we analyzed 10 patients with primary nephrotic syndrome representing proteinuric CKD with preserved GFR (>60 ml / min rau 1.73 m2) thiab 15 tus neeg mob CKD nrog nephrotic-ntau proteinuria thiab GFR<60 ml/min="" per="" 1.73="">². Cov yam ntxwv ntawm tus neeg mob tau pom nyob rau hauv Table 1. Cov kab mob raum-txuas ntxiv rau ntshav qab zib, raws li tau hais los ntawm hemoglobin concentration.<13.5 g/dl="" in="" men="" and=""><12 g/dl="" in="" women,="" was="" observed="" in="" 4="" of="" the="" 10="" primary="" nephrotic="" patients="" (red="" triangles="" in="" figure="" 7),="" whereas="" 14="" of="" 15="" ckd="" patients="" with="" nephrotic-range="" proteinuria="" and="" reduced="" gfr="" were="" anemic="" (figure="" 7a).="" in="" the="" latter="" group,="" plasma="" epo="" concentrations="" and="" reticulocyte="" production="" index="" were="" not="" increased="" (figure="" 7b="" and="" c),="" consistent="" with="" reduced="" erythropoiesis.="" in="" fluorescence-activated="" cell="" sorting="" analysis,="" primary="" nephrotic="" patients="" and="" patients="" with="" advanced="" ckd="" had="" a="" higher="" rate="" of="" ps-exposing="" cells="" (mean,="" 1.0%="" 0.3%="" and="" 1.4%="" 0.7%,="" respectively)="" compared="" with="" healthy="" subjects="" (mean,="" 0.6%="" 0.1%;="" figure="" 7d).="" rbc="" cell="" death="" in="" patients="" with="" primary="" nephrotic="" syndrome="" and="" advanced="" ckd="" was="" triggered="" by="" higher="" levels="" of="" reactive="" oxygen="" species="" (figure="" 7e)="" and="" increased="" ceramide="" levels="" (figure="" 7f).="" augmented="" intracellular="" calcium="" concentration="" was="" found="" in="" patients="" with="" advanced="" ckd="" (figure="">

Tib neeg RBCs los ntawm cov neeg mob uas muaj thawj nephrotic syndrome thiab CKD siab heev tau pom cov kev hloov pauv ntawm morphologic, raws li tau pom hauv cov qauv nas (Figures 4c thiab 7j-l thiab Cov Duab Ntxiv S4A). Txawm hais tias RBC morphology yog ib txwm muaj nyob rau hauv kev tswj hwm, cov neeg mob anemic nrog thawj tus mob nephrotic syndrome thiab cov neeg mob CKD siab heev muaj ntau cov teardrop hlwb (cov duab peb sab dub) thiab echinocytes (dub crosses) (Daim duab 7k thiab l). Tsis tas li ntawd, cov hom phiaj tau tshwm sim hauv thawj cov neeg mob ntshav qab zib nephrotic uas muaj ntshav qab zib thiab hauv cov neeg mob uas muaj CKD siab heev (liab hla; Daim duab 7k thiab l). Txhua pawg neeg mob, suav nrog cov neeg mob thawj nephrotic uas tsis muaj ntshav qab zib, muaj kev nce ntxiv ntawm spherocytes (xiav xub; Daim duab 7j–l). Txhawm rau txheeb xyuas qhov deformability ntawm tib neeg RBCs, ektacytometry tau ua. Hauv kev sib piv rau kev tswj hwm kev noj qab haus huv, qhov siab tshaj plaws deformability (EImax) tau txo qis hauv cov neeg mob siab CKD (Daim duab 7h); EImax zoo li qis dua hauv cov neeg mob uas muaj thawj nephrotic syndrome yam tsis tau ncav cuag qhov tseem ceeb (Daim duab 7h). Qhov tsis muaj SS1/2, Omin, Ohyper, thiab EImax ntawm isotonicity tsis muaj qhov sib txawv ntawm kev tswj hwm kev noj qab haus huv, thawj cov neeg mob ntshav qab zib, thiab cov neeg mob uas muaj CKD siab heev (Cov duab ntxiv S8A-D).

Cov txiaj ntsig Cistancheraum thiab pab nrog CKD.

Kev sib tham

Txoj kev tshawb no nthuav tawm cov txheej txheem pathophysiological tshiab uas ua rau muaj kab mob hauv lub raum-txuas ntxiv ntshav hauv 2 murine qauv ntawm proteinuric.mob raumnrog kev puas tsuaj loj heevlub raum ua haujlwm. Peb txoj kev tshawb fawb qhia tau hais tias nyob rau hauv cov qauv no, anemia yog tshwm sim los ntawm ib tug txo RBC lifespan tshwm sim los ntawm raug rau PS thiab ceev phagocytic clearance. Intriguingly, anemia nyob rau hauv cov nas no tau tsim txawm tias txhawb erythropoiesis, qhia tias txo RBC lifespan, los ntawm nce RBC cell tuag, tej zaum yuav yog ib qho kev piav qhia rau cov kev tshawb pom no. Contrary to CKD cov neeg mob uas muaj ntshav qab zib (Daim duab 77), ob tus nas qauv tau pom los ntawm kev nce ntshav plasma EPO concentration. Qhov no tuaj yeem tshwm sim los ntawm kev khaws cia ntawm EPO-secreting peev xwm hauv cov qauv no uas tej zaum yuav cia cov EPO-secreting hlwb nyob rau hauv interstitium ntawm lub raum. Txawm li cas los xij, qhov nce EPO secretion hauv cov qauv no, txawm li cas los xij, tsis ua rau qhov kev txiav txim siab tias RBC cell tuag yog ib qho tseem ceeb hauv cov kab mob hauv lub raum-txoj kev mob ntshav qab zib. Ntawm qhov tsis sib xws, stimulation ntawm erythropoiesis los ntawm kev nce EPO secretion tuaj yeem suav tias yog ib qho nyiaj them rov qab rau kev nce RBC kev tuag vim yograum tsis ua haujlwmhauv cov qauv no. Nyob rau hauv cov kab no, nce extramedullary erythropoiesis nrog nce spleen ntim tsis ntev los no tau pom nyob rau hauv lwm tus qauv proteinuric nas nrog anemia.³⁸

Hauv cov neeg mob uas muaj proteinuric CKD thiab concomitant anemia, peb kuj tau pom muaj feem pua ​​​​ntawm PS-exposing RBCs nrog rau qib siab ntawm cov pa oxygen reactive thiab ceramide. Qhov no qhia tau hais tias nrawm RBC kev tuag tuaj yeem koom nrog hauv pathogenesis ntawm cov kab mob hauv lub raum-koom nrog ntshav qab zib hauv tib neeg CKD. Plasma EPO concentrations thiab reticulocyte ntau lawm Performance index tsis tau nce nyob rau hauv anemic CKD cov neeg mob, taw qhia kom txo erythropoiesis, uas nyob rau hauv kev hais kwv txhiaj nrog RBC kev tuag yuav tsum ua rau hnyav rau lub raum kab mob - txuam nrog anemia. Cov laj thawj rau qhov poob ntawm EPO tso tawm ntawm lub raum hauv tib neeg CKD tseem tsis paub meej. Zoo kawg nkaus, txawm hais tias tsis yog txhua tus neeg mob uas muaj GFR ib txwm muaj ntshav qab zib, cov neeg uas muaj GFR txo qis yog tag nrho cov anemic, taw qhia txog qhov cuam tshuam ntawm kev ua haujlwm ntev thiab siab CKD. Qhov tseem ceeb, qhov txheeb ze EPO tsis txaus hauv CKD tuaj yeem kov yeej los ntawm kev siv chav kawm tshiab ntawm prolyl hydroxylase inhibitors,³⁹qhia perturbed oxygen sensing raws li ib tug ua tau rau EPO hyposecretion.

Cistanchetxhim kholub raum ua haujlwms thiab pab nrog CKD.

Peb cov ntaub ntawv qhia tau hais tias txo qis RBC deformability nyob rau hauv ob qho tib si nas qauv ntawm proteinuric nephropathy, uas tej zaum yuav ncaj qha cuam tshuam rau nce cytoplasmic Ca2þ theem.⁴⁰ Ua ke, cov txheej txheem no tuaj yeem ua haujlwm hauv kev hais kwv txhiaj los pab txhawb kev cuam tshuam ntawm RBC cell tuag thiab tshem tawm ntawm senescent thiab raug mob RBCs los ntawm cov ntshav ncig.¹⁵Tsis tas li ntawd, peb tau pom cov metabolic reprogramming nyob rau hauv cov hlwb, qhia txog oxidative kev nyuaj siab thiab membrane lipid remodeling. Txawm hais tias CoA thiab acyl-CoA tsis raug ntsuas ncaj qha hauv cov qauv no, lawv tau hloov pauv hauv RBCs rau acylcarnitines los ntawm carnitine palmitoyl transferase.³⁶Kev sib sau ua ke ntawm cov chav kawm tom kawg qhia txog kev ua kom cov txheej txheem no hauv nephropathy, vim tias cov metabolites tsis tau nkag mus thoob plaws RBC daim nyias nyias.⁴¹ Hauv kev txhawb nqa ntxiv, peb tau pom qhov sib txuam hauv ob qho tib si qauv ntawm CoA precursors, suav nrog pantothenate, uas tau coj mus rau⁴²thiab metabolized⁴³los ntawm RBCs, nyob rau hauv parallel mus nce dawb fatty acids thiab txo dawb carnitine. Interestingly, peb yav tas los pom tias cov kev hloov pauv no tshwm sim hauv kev koom nrog supraphysiologic qib ntawm intracellular Ca2þ.¹⁶Txawm hais tias cov txiaj ntsig tau tsim tawm ex vivo, peb tshaj tawm cov lus teb zoo sib xws hauv vivo. Tsis tas li ntawd, acylcarnitines muaj peev xwm ncaj qha hloov cov khoom ntawm cov membrane⁴⁴thiab cuam tshuam nrog RBC deformability^,45Nrog rau osmotic thiab oxidative hemolysis.⁴⁶Unconjugated dawb carnitine, txhawb cov membrane deformability los ntawm kev sib kho ntawm kev sib cuam tshuam ntawm daim nyias nyias proteins.⁴⁷ Peb qhov kev soj ntsuam ntawm qhov txo qis ntawm carnitine hauv RBCs los ntawm cov nas nrog nephropathy, txawm tias yog vim muaj kev noj ntau ntxiv rau cov cim ntawm acylcarnitines, tuaj yeem ua rau muaj qhov tsis zoo rheological uas peb tau pom nyob rau hauv tib lub sijhawm.

Peb qhov kev tshawb pom qhia tias muaj cov txheej txheem uas ua rau RBC tuag hauv cov nas nrog DIN thiab podocin tsis txaus, uas tej zaum yuav cuam tshuam rau ob qho tib si nephrotic-ntau proteinuria thiab, qhov tseem ceeb tshaj, kev loj hlob ntawm qhov hnyav.raum tsis ua haujlwmnyob rau hauv cov qauv nas pom los ntawm hnub 20 rau. Hauv tib neeg, qib siab CKD nrog txo GFR yog qhov ua tau zoo ntawm kev mob ntshav qab zib,⁴⁸thiab stimulation ntawm RBC tuag yuav muaj feem xyuam rau lub uremic milieu. Ib qho yuav tsum lees paub tias hauv CKD qib siab, ntau yam thiab kev cuam tshuam tuaj yeem tuaj yeem ua si thiab txhawb cov kab mob hauv lub raum - cuam tshuam txog ntshav ntshav. Kev koom tes ntawm cov proteinuria hnyav rau kev txhawb nqa ntawm RBC kev tuag tseem tsis tau paub meej, tab sis, txawm tias tsis muaj pov thawj, yuav muaj feem cuam tshuam rau cov zis, xws li transferrin lossis lwm tus tswj RBC metabolism.⁴⁹Txog tam sim no, tam sim no kev kho mob raum mob ntshav qab zib muaj feem xyuam rau kev nce erythropoiesis los ntawm kev hloov pauv hlau lossis EPO,⁵⁰los ntawm kev siv qhov ncauj hypoxia-inducible yam protein stabilizers,⁵¹los yog los ntawm qhov ncauj los yog iv hlau tswj.⁵²Txawm li cas los xij, cov kev kho mob no tsis xav txog kev nce RBC kev tuag. Hauv kev tshawb fawb hla dhau los hauv cov neeg mob hemodialysis thiab peritoneal dialysis, peb pom tias cov neeg mob uas muaj feem pua ​​​​ntawm PS-exposing RBCs tau kho nrog ntau dua EPO koob tshuaj.¹⁴ Yog li ntawd, amelioration ntawm RBC cell tuag tau cog lus tias yuav yog ib txoj hauv kev kho tau zoo hauv kev kho mob raum-cuam tshuam ntshav ntshav. Nyob rau hauv cov ntsiab lus no, cov nyhuv inhibitory ntawm ntau yam tshuaj pharmacological ntawm RBC cell death53 yuav tsum tau kawm ntxiv txog tib neeg thiab tsiaj txhu.

Hauv kev xaus, kev hloov pauv ntawm cov cellular metabolism ua rau RBC tsis ua haujlwm, txhim kho RBC kev tuag, thiab yog li ntshav ntshav hauv nas qauv ntawm proteinuric CKD, txawm tias nce qib EPO. Qhov kev tshawb pom ntawm qhov kev tshawb fawb no tuaj yeem piav qhia txog cov txheej txheem ntawm kev mob ntshav qab zib nrog CKD hauv tib neeg.

Cistanche cov txiaj ntsiglub raum ua haujlwm thiab pab nrog CKD.

Qhia tawm

Txawm hais tias tsis muaj feem cuam tshuam nrog cov ntsiab lus ntawm cov ntawv, ADA thiab TN yog tus tsim ntawm Omix Technologies, Inc. Tag nrho lwm tus kws sau ntawv tshaj tawm tsis muaj kev nyiam sib tw.

DATA STATEMENT

Cov ntaub ntawv yuav muaj nyob rau ntawm qhov kev thov tsim nyog.

TXOJ CAI

Cov kws sau ntawv lees paub cov kws tshaj lij kev pabcuam ntawm Andrea Janessa. Cov kev tshawb fawb no tau txais kev txhawb nqa los ntawm German Research Foundation rau RB (BI 2149/2-1) thiab FA (AR 1092/2-2). LS tau txais kev txhawb nqa los ntawm Interdisziplinäres Zentrum für Klinische Forschung (IZKF) nyiaj pab los ntawm cov kws kho mob ntawm Tübingen University. SMQ tau txais kev txhawb nqa los ntawm cov peev txheej los ntawm Canadian Blood Services. Raws li ib qho xwm txheej ntawm tsoomfwv Canadian nyiaj txiag, daim ntawv tshaj tawm no yuav tsum muaj cov lus hais "Cov kev xav tau hais hauv no tsis tas yuav sawv cev rau qhov kev pom ntawm tsoomfwv Canada."

AUTHOR CONTRIBUTIONS

RB thiab FA tsim qhov kev tshawb fawb. Kev sau cov ntaub ntawv tau ua los ntawm RB, TN, MG, TD, DE, MW, LS, MX, JMB, MZK, KO, LK, IG-M, thiab BF.

Kev txheeb xyuas txheeb cais tau ua los ntawm RB, TN, MG, TD, LS, JMB, LK, IG-M, thiab ADh; thiab cov duab tau tsim los ntawm RB, TN, MZK, IG-M, LQ-M, BF, thiab ADh. RB, TN, ADA, MG, BNB, LS, AS, TB, MS, ALB, FG, SMQ,

thiab FA tau txhais cov ntaub ntawv. Cov ntawv sau tau sau, tshuaj xyuas, thiab kho los ntawm RB, TN, ADA, MG, BNB, TB, ALB, FG, SMQ, thiab FA.

SUPPLEMENTARY KHOOM

Cov ntaub ntawv ntxiv (PDF)

Cov khoom siv ntxiv thiab cov txheej txheem.

Daim duab S1. Kev sim tsim cov kev tshawb fawb hauv 129S1/SvImJ thiab Nphs2Dipod nas.

Daim duab S2. Kev tshem tawm ntawm podocin qhia thiab cov cim qhia ntawm nephrotic syndrome hauv Nphs2Dipod nas.

Daim duab S3. Txo cov qe ntshav liab ciaj sia nyob hauv kev sim nephrotic syndrome hauv Nphs2Dipod nas.

Daim duab S4. Hloov morphology thiab txo deformability ntawm cov qe ntshav liab hauv Nphs2Dipod nas.

Daim duab S5. Metabolomics qhia txog kev tsub zuj zuj ntawm oxidative kev nyuaj siab thiab ua kom cov membrane lipid remodeling hauv cov qe ntshav liab hauv Nphs2Dipod nas.

Daim duab S6. Metabolomics qhia txog kev hloov pauv cov metabolism hauv cov qe ntshav liab tau los ntawm 129S1 / SvImJ nas.

Daim duab S7. Metabolomics qhia txog kev hloov pauv cov metabolism hauv cov qe ntshav liab tau txais los ntawm Nphs2Dipod nas.

Daim duab S8. Shear stress ntawm ib nrab ntawm qhov siab tshaj plaws ntawm cov qe ntshav liab (RBC) deformability thiab RBC osmotic rhiab heev tsis muaj qhov sib txawv hauv thawj nephrotic syndrome thiab cov neeg mob siab mob raum mob (CKD).

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THIAB thiab lwm yam.