Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models

被引：17

作者：

Yang, Ru-chun ^{[1
]}

Zhu, Xiao-ling ^{[1
]}

Wang, Jun ^{[1
]}

Wan, Feng ^{[1
]}

Zhang, Hua-qin ^{[1
]}

Lin, Yi ^{[1
]}

Tang, Xuan-li ^{[1
]}

Zhu, Bin ^{[1
]}

机构：

[1] Hangzhou Hosp Tradit Chinese Med, Key Lab Zhejiang Prov Management Kidney Dis, Dept Nephrol, Tiyuchang Rd 453, Hangzhou 310007, Zhejiang, Peoples R China

来源：

BMC NEPHROLOGY | 2018年 / 19卷

基金：

中国国家自然科学基金;

关键词：

BMSC; FSGS; MMP9; TIMP-1; Proinflammatory cytokines; Rat; CHRONIC KIDNEY-DISEASE; DIFFERENTIATION;

D O I：

10.1186/s12882-018-1137-5

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundFocal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression.MethodsA rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF- were examined via RT-PCR.ResultsThe isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-.ConclusionsBMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.

引用

页数：10