Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling

間葉系幹細胞は炎症抑制およびTGF-β1シグナルの抑制を介し腹膜線維化を改善させる

上野 敏憲

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have regenerative capability and exert paracrine actions on damaged tissues. Since peritoneal fibrosis is a serious complication of peritoneal dialysis, we tested whether MSCs suppress this using a chlorhexidine gluconate model in rats. Although MSCs isolated from green fluorescent protein? positive rats were detected for only 3 days following their injection, immunohistochemical staining showed that MSCs suppressed the expression of mesenchymal cells, their effects on the deposition of extracellular matrix proteins, and the infiltration of macrophages for 14 days. Moreover, MSCs reduced the functional impairment of the peritoneal membrane. Cocultures of MSCs and human peritoneal mesothelial cells using a Transwell system indicated that the beneficial effects of MSCs on the glucose-induced upregulation of transforming growth factor-β1(TGF-β1) and fibronectin mRNA expression in the human cells were likely due to paracrine actions. Preincubation in MSC-conditioned medium suppressed TGFβ1- induced epithelial-to-mesenchymal transition, a-smooth muscle actin, and the decrease in zonula occludens-1 in cultured human peritoneal mesothelial cells. Although bone morphogenic protein 7 was not detected, MSCs secreted hepatocyte growth factor and a neutralizing antibody to this inhibited TGF-β1 signaling. Thus, our findings imply that MSCs ameliorate experimental peritoneal fibrosis by suppressing inflammation and TGF-β1 signaling in a paracrine manner.

epithelial-to-mesenchymal transition

hepatocyte growth factor

mesenchymal stem cells

peritoneal fibrosis

transforming growth factor-β1

医学 [ 490 ]

英語

Copyright(c) by Author

[作成日] 2014-11-21

Toshinori Ueno, Ayumu Nakashima, Shigehiro Doi, Takeshi Kawamoto, Kiyomasa Honda, Yukio Yokoyama, Toshiki Doi, Yukihito Higashi, Noriaki Yorioka, Yukio Kato, Nobuoki Kohno and Takao Masaki; Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-β1 signaling; Kidney International (2013) 84, 297-307, published online 13 March 2013 (doi: 10.1038/ki.2013.81) ～を参照している

[DOI] http://dx.doi.org/10.1038/ki.2013.81 ～を参照している

広島大学