Revista de Ciências Biomédicas e Farmacêuticas

Association of Fibrotic and Apoptotic Markers in Renal Tubulointerstitial Fibrosis Induced by Unilateral Ureteral Obstruction

Abstract

Sahar Hamed, Nashwa Barakat, Mohamed Sobh, Nahla Anber, Basma Hamed and Fatema Moustafa

Many apoptotic and fibrotic markers are known to be important in the development of renal fibrosis. In Unilateral Ureteral Obstruction (UUO) the Obstructed Kidney (OK) develops fibrosis, while the Contralateral (CL) does not. In this study we investigated the gene expression of different apoptotic and fibrotic molecules which may affect fibrosis developments due to UUO. UUO was prepared under isoflurane anesthesia, and the animals were sacrificed after 3, 7 and 14 days post UUO. UUO caused hydronephrosis, dilation of renal tubules, loss of parenchymal thickness, apoptosis and fibrosis. Damage was most severe in mice sacrificed after 14 days of UUO, while both 3 and 7 days groups showed considerably milder hydronephrosis, no tubular necrosis, and less tubular dilation. We detected increased levels of transforming growth factor β (TGF-β) and alpha-smooth muscle actin (α-SMA), Matrix metalloproteinase 2 (MMP2) and MMP9 (fibroblast activation marker) and TNF as apoptotic marker in the kidney tissue of UUO mice relative to the control UUO mice. This increase was confirmed by immunohistochemistry and gene expression as well. In conclusion, we found that the different pro-fibrotic molecules, α-SMA, TGF-β, MMP2, MMP9, Fibronectin and pro-apoptotic molecule, TNF expression were increased in UUO mouse kidney compared to contralateral or sham kidney. This increase was found to be time dependent.