title: Epithelial cells as active player in fibrosis: findings from an in vitro model.
abstract: Kidney fibrosis, a scarring of the tubulo-interstitial space, is due to activation of interstitial myofibroblasts recruited locally or systemically with consecutive extracellular matrix deposition. Newly published clinical studies correlating acute kidney injury (AKI) to chronic kidney disease (CKD) challenge this pathological concept putting tubular epithelial cells into the spotlight. In this work we investigated the role of epithelial cells in fibrosis using a simple controlled in vitro system. An epithelial/mesenchymal 3D cell culture model composed of human proximal renal tubular cells and fibroblasts was challenged with toxic doses of Cisplatin, thus injuring epithelial cells. RT-PCR for classical fibrotic markers was performed on fibroblasts to assess their modulation toward an activated myofibroblast phenotype in presence or absence of that stimulus. Epithelial cell lesion triggered a phenotypical modulation of fibroblasts toward activated myofibroblasts as assessed by main fibrotic marker analysis. Uninjured 3D cell culture as well as fibroblasts alone treated with toxic stimulus in the absence of epithelial cells were used as control. Our results, with the caveats due to the limited, but highly controllable and reproducible in vitro approach, suggest that epithelial cells can control and regulate fibroblast phenotype. Therefore they emerge as relevant target cells for the development of new preventive anti-fibrotic therapeutic approaches.
authors: Institute of Clinical Pathology, University Hospital Geneva, Geneva, Switzerland.
authors: Solange
authors: S
authors: Moll
authors: Martin
authors: M
authors: Ebeling
authors: Franziska
authors: F
authors: Weibel
authors: Annarita
authors: A
authors: Farina
authors: Andrea
authors: A
authors: Araujo Del Rosario
authors: Jean Christophe
authors: JC
authors: Hoflack
authors: Silvia
authors: S
authors: Pomposiello
authors: Marco
authors: M
authors: Prunotto
mesh_terms: D002460:Cell Line; D060833:Cellular Microenvironment / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*
chemical_list: D002945:Cisplatin