Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury

Yi Ting Chen, Yu Ting Chang, Szu Yu Pan, Yu Hsiang Chou, Fan Chi Chang, Pei Ying Yeh, Yuan Hung Liu, Wen Chih Chiang, Yung Ming Chen, Kwan Dun Wu, Tun Jun Tsai, Jeremy S. Duffield, Shuei Liong Lin

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63 Citations (Scopus)

Abstract

Fibrosis of the peritoneal cavity remains a serious, life-threatening problem in the treatment of kidney failure with peritoneal dialysis. The mechanism of fibrosis remains unclear partly because the fibrogenic cells have not been identified with certainty. Recent studies have proposed mesothelial cells to be an important source of myo fibroblasts through the epithelial -mesenchymal transition; however, confirmatory studies in vivo are lacking. Here, we show by inducible genetic fate mapping that type I collagen-producing submesothelial fibroblasts are specific progenitors of α-smooth muscle actin- positive myofibroblasts that accumulate progressively in models of peritoneal fibrosis induced by sodium hypochlorite, hyperglycemic dialysis solutions, or TGF-β1. Similar genetic mapping of Wilms' tumor-1-positive mesothelial cells indicated that peritoneal membrane disruption is repaired and replaced by surviving mesothelial cells in peritoneal injury, and not by submesothelial fibroblasts. Although primary cultures of mesothelial cells or submesothelial fibroblasts each expressed α-smooth muscle actin under the influence of TGF-β1, only submesothelial fibroblasts expressed α-smooth muscle actin after induction of peritoneal fibrosis in mice. Furthermore, pharmacologic inhibition of the PDGF receptor, which is expressed by submesothelial fibroblasts but not mesothelial cells, attenuated the peritoneal fibrosis but not the remesothelialization induced by hypochlorite. Thus, our data identify distinctive fates for injured mesothelial cells and submesothelial fibroblasts during peritoneal injury and fibrosis.

Original languageEnglish
Pages (from-to)2847-2858
Number of pages12
JournalJournal of the American Society of Nephrology
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

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