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

Research output: Contribution to journalArticle

56 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

Fingerprint

Peritoneal Fibrosis
Fibroblasts
Wounds and Injuries
Smooth Muscle
Actins
Fibrosis
Hypochlorous Acid
Platelet-Derived Growth Factor Receptors
Sodium Hypochlorite
Epithelial-Mesenchymal Transition
Primary Cell Culture
Myofibroblasts
Wilms Tumor
Dialysis Solutions
Peritoneal Cavity
Peritoneal Dialysis
Collagen Type I
Treatment Failure
Renal Insufficiency
Membranes

ASJC Scopus subject areas

  • Nephrology

Cite this

Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury. / Chen, Yi Ting; Chang, Yu Ting; Pan, Szu Yu; Chou, Yu Hsiang; Chang, Fan Chi; Yeh, Pei Ying; Liu, Yuan Hung; Chiang, Wen Chih; Chen, Yung Ming; Wu, Kwan Dun; Tsai, Tun Jun; Duffield, Jeremy S.; Lin, Shuei Liong.

In: Journal of the American Society of Nephrology, Vol. 25, No. 12, 01.12.2014, p. 2847-2858.

Research output: Contribution to journalArticle

Chen, YT, Chang, YT, Pan, SY, Chou, YH, Chang, FC, Yeh, PY, Liu, YH, Chiang, WC, Chen, YM, Wu, KD, Tsai, TJ, Duffield, JS & Lin, SL 2014, 'Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury', Journal of the American Society of Nephrology, vol. 25, no. 12, pp. 2847-2858. https://doi.org/10.1681/ASN.2013101079
Chen, Yi Ting ; Chang, Yu Ting ; Pan, Szu Yu ; Chou, Yu Hsiang ; Chang, Fan Chi ; Yeh, Pei Ying ; Liu, Yuan Hung ; Chiang, Wen Chih ; Chen, Yung Ming ; Wu, Kwan Dun ; Tsai, Tun Jun ; Duffield, Jeremy S. ; Lin, Shuei Liong. / Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 12. pp. 2847-2858.
@article{cf16646252254862b52c64ae5f2df6b8,
title = "Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury",
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.",
author = "Chen, {Yi Ting} and Chang, {Yu Ting} and Pan, {Szu Yu} and Chou, {Yu Hsiang} and Chang, {Fan Chi} and Yeh, {Pei Ying} and Liu, {Yuan Hung} and Chiang, {Wen Chih} and Chen, {Yung Ming} and Wu, {Kwan Dun} and Tsai, {Tun Jun} and Duffield, {Jeremy S.} and Lin, {Shuei Liong}",
year = "2014",
month = "12",
day = "1",
doi = "10.1681/ASN.2013101079",
language = "English",
volume = "25",
pages = "2847--2858",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "12",

}

TY - JOUR

T1 - Lineage tracing reveals distinctive fates for mesothelial cells and submesothelial fibroblasts during peritoneal injury

AU - Chen, Yi Ting

AU - Chang, Yu Ting

AU - Pan, Szu Yu

AU - Chou, Yu Hsiang

AU - Chang, Fan Chi

AU - Yeh, Pei Ying

AU - Liu, Yuan Hung

AU - Chiang, Wen Chih

AU - Chen, Yung Ming

AU - Wu, Kwan Dun

AU - Tsai, Tun Jun

AU - Duffield, Jeremy S.

AU - Lin, Shuei Liong

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923861810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923861810&partnerID=8YFLogxK

U2 - 10.1681/ASN.2013101079

DO - 10.1681/ASN.2013101079

M3 - Article

VL - 25

SP - 2847

EP - 2858

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 12

ER -