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Stem Cell Res Ther. 2018 Jan 12;9(1):7. doi: 10.1186/s13287-017-0760-6.

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.

Author information

1
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
2
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China.
3
Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2 RD, Yuzhong District, Chongqing, 400014, China. dingfengxia305@163.com.
4
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China. dingfengxia305@163.com.
5
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.

Abstract

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-α, IL-6, and IL-1β 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-β1-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-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB 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-κB signaling pathway activation.

KEYWORDS:

Conditioned medium; Fibrosis; Mesenchymal stem cell; Tubulointerstitial inflammation

PMID:
29329595
PMCID:
PMC5767037
DOI:
10.1186/s13287-017-0760-6
[Indexed for MEDLINE]
Free PMC Article

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