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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2014 ; 25
(12
): 2847-58
Nephropedia Template TP
gab.com Text
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Lineage tracing reveals distinctive fates for mesothelial cells and
submesothelial fibroblasts during peritoneal injury
#MMPMID24854266
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
J Am Soc Nephrol
2014[Dec]; 25
(12
): 2847-58
PMID24854266
show ga
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 ?-smooth muscle actin-positive
myofibroblasts that accumulate progressively in models of peritoneal fibrosis
induced by sodium hypochlorite, hyperglycemic dialysis solutions, or TGF-?1.
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 ?-smooth muscle actin under the influence of TGF-?1, only
submesothelial fibroblasts expressed ?-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.