Epithelial-to-mesenchymal transition in fibrosis: collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition.

Experimental cell research ·Vol. 319 ·No. 19 ·2014-02-13

Hosper Nynke A, van den Berg Paul P, de Rond Saskia, Popa Eliane R, Wilmer Martijn J, Masereeuw Rosalinde, Bank Ruud A

Abstract

The hallmark of fibrosis is an accumulation of fibrillar collagens, especially of collagen type I. There is considerable debate whether in vivo type II epithelial-to-mesenchymal transition (EMT) is involved in organ fibrosis. Lineage tracing experiments by various groups show opposing data concerning the relative contribution of epithelial cells to the pool of myofibroblasts. We hypothesized that EMT-derived cells might directly contribute to collagen deposition. To study this, EMT was induced in human epithelial lung and renal cell lines in vitro by means of TGF-β1 stimulation, and we compared the collagen type I (COL1A1) expression levels of transdifferentiated cells with that of myofibroblasts obtained by TGF-β1 stimulation of human dermal and lung fibroblasts. COL1A1 expression levels of transdifferentiated epithelial cells appeared to be at least one to two orders of magnitude lower than that of myofibroblasts. This was confirmed at immunohistochemical level: in contrast to myofibroblasts, collagen type I deposition by EMT-derived cells was not or hardly detectable. We postulate that, even when type II EMT occurs in vivo, the direct contribution of EMT-derived cells to collagen accumulation is rather limited.

Keywords

ACTA2 BEAS-2B BSA CDH1 COL1A1 COL3A1 Collagen deposition E-cadherin ECM EMT EPCAM Epithelial cells Epithelial to mesenchymal transition FCS Fibrosis HDF HK-2 HLF Myofibroblasts NHS PBS TAGLN TGFβ-1 VIM alpha-actin-2 (alpha smooth muscle actin) bovine serum albumin ciPTEC collagen type I collagen type III conditionally immortalized human proximal tubule cells epithelial cell adhesion molecule epithelial-to-mesenchymal transition extracellular matrix fetal calf serum human dermal fibroblasts human lung bronchial epithelial cells human lung fibroblasts human renal proximal tubule epithelial cells normal human serum phosphate buffered saline qRT-PCR quantitative Reverse Transcription polymerase chain reaction transforming growth factor beta 1 transgelin (smooth muscle protein 22-alpha) vimentin

Article Info

Journal

Experimental cell research

Abbr.

Exp Cell Res

ISSN

0014-4827

DOI

10.1016/j.yexcr.2013.07.014

Published

2014-02-13

Indexed

2013-11-01

Updated

2013-11-01

Language

English

Country/Region

United States

NLM ID

0373226

External Links

PubMed source DOI: 10.1016/j.yexcr.2013.07.014 View journal details

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Epithelial-to-mesenchymal transition in fibrosis: collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition.

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