Treating Type 2 Diabetic Nephropathy by Down-regulating NOX4 to Inhibit the Oxidative Stress Pathway in Mesenchymal Stem Cells
10.13865/j.cnki.cjbmb.2025.03.1425
- VernacularTitle:间充质干细胞影响NADHP氧化酶4抑制氧化应激通路治疗2型糖尿病肾病
- Author:
Shu-Qi FENG
1
;
Guo-Rong JIN
1
;
Qun-Hang XUE
1
;
Min HE
1
;
Ze-Hang WANG
1
;
Jia-Xin YAO
1
;
Long CHEN
1
;
Yu-Jiao WANG
1
;
An-Xiu ZHANG
1
;
Sheng HE
1
;
Bing-Rui ZHOU
1
;
Jun XIE
1
Author Information
1. 山西医科大学基础医学院生物化学与分子生物学教研室 出生缺陷与细胞再生山西省重点实验室 煤炭环境致病与预防教育部重点实验室 山西省临床细胞治疗转化试点基地,太原 030001
- Publication Type:Journal Article
- Keywords:
diabetic nephropathy(DN);
human umbilical cord derived mesenchymal stem cells(hUC-MSCs);
oxidative stress;
NADPH oxidase 4(NOX4);
thioredoxin-interacting protein(TXNIP)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(5):730-740
- CountryChina
- Language:Chinese
-
Abstract:
Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.
