Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via the TLR4/NF-κB signaling pathway in vivo and in vitro

被引：116

作者：

Liu, Bo ^{[2
,3
]}

Ding, Fengxia ^{[1
,2
]}

Hu, Dong ^{[2
]}

Zhou, Yu ^{[2
]}

Long, Chunlan ^{[2
]}

Shen, Lianju ^{[2
]}

Zhang, Yuanyuan ^{[4
]}

Zhang, Deying ^{[2
,3
]}

Wei, Guanghui ^{[3
]}

机构：

[1] Chongqing Med Univ, Childrens Hosp, Dept Resp Med, 136 Zhongshan 2 RD Yuzhong Dist, Chongqing 400014, Peoples R China

[2] Chongqing Int Sci & Technol Cooperat Ctr Child De, Chongqing Key Lab Pediat, Chongqing Key Lab Children Urogenital Dev & Tissu, Key Child Dev & Disordes,Minist Educ, Chongqing 400014, Peoples R China

[3] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China

[4] Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27101 USA

来源：

STEM CELL RESEARCH & THERAPY | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

Mesenchymal stem cell; Conditioned medium; Tubulointerstitial inflammation; Fibrosis; ACUTE KIDNEY INJURY; NF-KAPPA-B; DISEASE; PREVALENCE; INDUCTION;

D O I：

10.1186/s13287-017-0760-6

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Background: Renal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis. Methods: Renal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-alpha, IL-6, and IL-1 beta in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-beta 1-induced epithelial-mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting. Results: hucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-beta 1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-kappa B signaling pathway in vivo and in vitro. Conclusions: Our results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-kappa B signaling pathway activation.

引用

页数：14

共 33 条

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