https://scholars.lib.ntu.edu.tw/handle/123456789/620855
標題: | Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury | 作者: | YI-TING CHEN YU-TING CHANG SZU-YU PAN YU-HSIANG CHOU FAN-CHI CHANG Yeh, Pei-Ying Liu, Yuan-Hung WEN-CHIH CHIANG YUNG-MING CHEN KWAN-DUN WU TUN-JUN TSAI Duffield, Jeremy S SHUEI-LIONG LIN |
關鍵字: | GROWTH-FACTOR-BETA; PERICYTE-MYOFIBROBLAST TRANSITION; TO-MESENCHYMAL TRANSITION; HEPATIC STELLATE CELLS; PULMONARY-FIBROSIS; EPITHELIAL-CELLS; KIDNEY FIBROSIS; GENE-EXPRESSION; IN-VITRO; DIALYSIS | 公開日期: | 十二月-2014 | 出版社: | AMER SOC NEPHROLOGY | 卷: | 25 | 期: | 12 | 起(迄)頁: | 2847 | 來源出版物: | Journal of the American Society of Nephrology : JASN | 摘要: | 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 myofibroblasts 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/620855 | ISSN: | 1046-6673 | DOI: | 10.1681/ASN.2013101079 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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