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Evidence that fibroblasts derive from epithelium during tissue fibrosis
Masayuki Iwano, … , Hirokazu Okada, Eric G. Neilson
Masayuki Iwano, … , Hirokazu Okada, Eric G. Neilson
Published August 1, 2002
Citation Information: J Clin Invest. 2002;110(3):341-350. https://doi.org/10.1172/JCI15518.
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Article Hematology

Evidence that fibroblasts derive from epithelium during tissue fibrosis

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Abstract

Research Article

Authors

Masayuki Iwano, David Plieth, Theodore M. Danoff, Chengsen Xue, Hirokazu Okada, Eric G. Neilson

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Figure 2

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Confocal microscopy images of merged stainings from kidney tissue follow...
Confocal microscopy images of merged stainings from kidney tissue following UUO. (a) Glomeruli from the contralateral kidneys in R26R × γGT.Cre mice 10 days after unilateral UUO have no reaction product. Unfloxed LacZ+ tubular epithelium stained red with anti-LacZ antibodies as evidence of recombination, and floxed LacZ– interstitial fibroblasts formed before day P7 stained green (FSP1+) with anti-FSP1 antibodies. ×630. (b) A representative cortical tubule undergoing EMT in kidney harvested 10 days after UUO stained with anti-FSP1 (green) and anti-LacZ (red). The merged confocal image demonstrates unfloxed FSP1+, LacZ+ epithelial cells staining yellow as double-positive cells. The tubule is disaggregating, with cellular elements assuming the shape of new interstitial FSP1+, LacZ+ fibroblasts. ×630. (c) Renal cortical interstitium from kidney harvested 10 days after UUO demonstrated that floxed FSP1+, LacZ– fibroblasts formed before day P7 were stained green (FSP1+), and adjacent and newly formed unfloxed FSP1+, LacZ+ fibroblasts (those created after day P7) stained yellow (double positive for FSP1 and LacZ) after local EMT. ×400. (d) Tubular EMT in kidney cortical tissue harvested 10 days after UUO demonstrated that floxed FSP1+, LacZ– fibroblasts formed before day P7 were stained green (FSP1+), some cortical FSP1+, LacZ+ tubular epithelial cells undergoing EMT were yellow (double positive for FSP1 and LacZ), and adjacent and newly formed, unfloxed FSP1+, LacZ+ fibroblasts stained yellow after EMT. ×630. (e) Day 10 UUO kidney sections stained with anti-LacZ (green) and (f) anti-HSP47 (red). (g) Merged kidney section in yellow demonstrates colocalization of HSP47 (collagen type I production) in unfloxed tubular LacZ+, HSP47+ epithelium undergoing EMT and in new unfloxed LacZ+, HSP47+ fibroblasts. ×400.
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