Renal fibrosis

Abstract

Tubulointerstitial renal fibrosis, characterized as a progressive detrimental connective tissue deposition on the kidney parenchyma, appears to be a harmful process leading inevitably to renal function deterioration, independently of the primary renal disease which causes the original kidney injury. Epithelial to Mesenchymal Transition (EMT) of tubular epithelial cells which are transformed to mesenchymal fibroblasts migrating to adjacent interstitial parenchyma constitutes the principal mechanism of renal fibrosis along with local and circulating cells. Proteinuria as well as hypoxia is included among the main mechanisms of EMT stimulation. TGFbeta-1 through the SMAD pathway is considered as the main modulator regulating the EMT molecular mechanism, probably in cooperation with hypoxia inducible factors. Hepatocyte Growth Factor (HGF) and Bone Morphogenetic Factor-7 (BMF-7) are inhibitory to EMT molecules which could prevent in experimental and clinical level the catastrophic process of interstitial fibrosis. Interesting data emerge indicating that HGF and BMF-7 administration prevents the peritoneal fibrosis of mesothelial cells.

Keywords: TGF-β; angiotensin II; cytokines; epithelial mesenchymal transition; fibrosis; growth factors; hypoxia; proteinuria.

Figure 1:. Renal fibrosis characterized by connective tissue expansion through tubulointerstitial parenchyma as well as by fibroblasts infiltration (arrows)

Figure 2:. Epithelial to Mesenchymal Transition (EMT). Epithelial cells in 3D culture (left) acquire new (mesenchymal) properties such as shape, cytoskeleton and migration capacity (right). Additionaly they are positive to smooth muscle cells a-actin