Expression of XBP1s in peritoneal mesothelial cells is critical for inflammation-induced peritoneal fibrosis.
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| Abstract |
Intraperitoneal inflammation is the most important determinant of peritoneal fibrosis in patients with long-term peritoneal dialysis (PD). Spliced x-box binding protein-1 (XBP1s), a major proximal effector of unfolded protein response (UPR) signaling, plays an indispensable role in inflammation. Our study demonstrated that the inflammatory factor interleukin-1β (IL-1β) dose- and time-dependently induced XBP1s upregulation and interleukin-6 (IL-6) secretion, as well as the expression of the fibrotic marker fibronectin. However, these effects were prevented by the IRE1 endonuclease inhibitor STF083010 since it time-dependently reduced IL-1β-induced Xbp1 mRNA splicing, XBP1s protein expression, inflammatory factor IL-6 secretion and the expression of the fibrotic marker fibronectin in human peritoneal mesothelial cells (HPMCs). The overexpression and knockdown of XBP1s in HPMCs had a similar effect on fibronectin expression. In a rat model of peritoneal inflammation, STF083010 significantly attenuated chlorhexidine digluconate-induced XBP1s and α-smooth muscle actin expression, as well as fibrotic tissue proliferation, in the peritoneum. Our results suggest that XBP1s is a strong pathogenic factor that mediates inflammation-induced peritoneal fibrosis in peritoneal dialysis.
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| Authors | An Liu, Qiong Song, Yong Zheng, Guoshuang Xu, Chen Huang, Shiren Sun, Lijie He, Lijuan Zhao, Meilan Zhou |
| Journal | Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 19043 (12 13 2019) ISSN: 2045-2322 [Electronic] England |
| PMID | 31836774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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