Mechanisms of progression and reversibility of the tubulointerstitial fibrosis

Abstract

The overload and the increase in the transport of proteins by proximal tubule cells is involved in the genesis of tubulointerstital fibrosis, a feature of the progressive renal disease with glomerular injury. The chronic inflammation due to the increase in traffic of proteins can also lead to a phenotypic change of the resident epithelial cells that are transformed into myofibroblasts, a process called epithelial-mesenchymal transition (EMT), contributing to the development of tubulointerstial fibrosis. TGF-b is major signaling molecule involved in the renal fibrosis. In contrast, the bone morphogenetic proteins (BMPs) bear antifibrogenic activity. BMPs are inhibited by a class of proteins called antagonists of BMPs and Gremlin is an important BMP antagonist with a potential role in the renal fibrosis mechanism. This study aims to evaluate the role of TGF-², BMP-7 and the Gremlin in EMT as well as in the reversal of renal fibrosis. These possibilities will be evaluated in in vitro model using proximal tubule cells treated with high concentrations of albumin and in in vivo model of proteinuric nephropathy induced by puromycin. (AU)