Premium
TGFβ1 induces epithelial–mesenchymal transition, but not myofibroblast transdifferentiation of human kidney tubular epithelial cells in primary culture
Author(s) -
Forino Monica,
Torregrossa Rossella,
Ceol Monica,
Murer Luisa,
Vella Manuela Della,
Prete Dorella Del,
D'Angelo Angela,
Anglani Franca
Publication year - 2006
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2006.00479.x
Subject(s) - transdifferentiation , myofibroblast , epithelial–mesenchymal transition , microbiology and biotechnology , human kidney , transforming growth factor , mesenchymal stem cell , transition (genetics) , kidney , epithelium , chemistry , biology , pathology , medicine , endocrinology , stem cell , fibrosis , biochemistry , gene
Summary The origin and fate of renal interstitial myofibroblasts (MFs), the effector cells of renal fibrosis, are still debated. Experimental evidence suggests that renal MFs derive from tubular epithelial cells throughout the epithelial–mesenchymal transition (EMT) process. Primary human tubular epithelial cells (HUTECs) were cultured for 4 and 6 days on plastic or type I collagen‐coated plates with 1, 5, 10 and 50 ng/ml of transforming growth factor β1 (TGFβ1). The EMT process was monitored by morphology and immunophenotyping for αSMA, cytokeratin 8–18, E‐cadherin, vimentin and collagen III. Quantitative comparative RT/PCR and real‐time PCR were used to evaluate the expression of collagen III and IV, fibronectin, tenascin, MMP‐2, CTGF, E‐cadherin and cadherin 11 genes, as well as those of the Smad signalling pathway. TGFβ1 was found capable of reactivating the mesenchymal programme switched off during tubulogenesis, but it induced no de novo expression of αSMA gene or myofibroblast phenotype. We demonstrate that the EMT process is conditioned by the extracellular matrix and characterized by TGFβ1‐driven Smad3 downregulation. Our study results suggest that TGFβ1 could function as a classic embryonal inducer, initiating a cascade of de‐differentiating events that might be further controlled by other factors in the cellular environment.