High glucose induces an activated state of partial epithelial-mesenchymal transition in human primary tubular cell cultures.

Autor: Barbara Torsello, Sofia De Marco, Silvia Bombelli, Ingrid Cifola, Ivana Morabito, Lara Invernizzi, Chiara Meregalli, Nicola Zucchini, Guido Strada, Roberto A Perego, Cristina Bianchi
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: PLoS ONE, Vol 18, Iss 2, p e0279655 (2023)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0279655
Popis: Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this study, we investigated the phenotypic and molecular EMT-like changes and the alteration of inflammatory and fibrogenic secretome induced by HG in human primary tubular cell cultures. Taking advantage of this in vitro cell model composed of proximal and distal tubular cells, we showed that HG-treated tubular cells acquired a fibroblast-like morphology with increased cytoplasmic stress fibers, maintaining the expression of the epithelial markers specific of proximal and distal tubular cells. HG increased Snail1, miRNA210 and Vimentin mesenchymal markers, decreased N-cadherin expression and migration ability of primary tubular cells, while E-cadherin expression and focal adhesion distribution were not affected. Furthermore, HG treatment of tubular cells altered the inflammatory cytokine secretion creating a secretome able to enhance the proliferation and migration of fibroblasts. Our findings show that HG promotes an activated state of partial EMT in human tubular primary cells and induces a pro-inflammatory and pro-fibrogenic microenvironment, supporting the active role of tubular cells in diabetic nephropathy onset.
Databáze: Directory of Open Access Journals
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