Downregulation of Profibrotic Gene Expression by Angiotensin Receptor Blockers

Abstract

Introduction: Chronic allograft nephropathy is characterized by interstitial fibrosis and tubular atrophy. The main players in the process of fibrosis are transforming growth factor-β (TGF-β) and miR-21 expression with a bidirectional interplay. This study aimed to evaluate the effects of angiotensin receptor type 1 antagonist, losartan, on peripheral blood and tissue expression of TGF-β and miR-21 and histologic findings in allograft biopsy in kidney transplant recipients.

Materials and methods: In a randomized controlled trial, 54 patients were enrolled and divided randomly into 2 groups. Group 1 was treated with a daily dose of 25 mg of losartan and group 2 was considered as control. Blood sampling was done at 48 hours posttransplantation and the 3rd and 6th months after transplantation for measurement of TGF-β RNA and miR-21. Protocol biopsy was performed at the 6th month posttransplantation for RNA extraction and histologic evaluation of interstitial fibrosis and tubular atrophy.

Results: Although patients were not different initially, those who underwent treatment with losartan had lower miR-21 and TGF-β levels in circulating PBMCs, and there was a decreasing trend in peripheral blood TGF-β levels during the 6-month follow-up period. Tissue expression of miR-21 and TGF-β was also considerably lower among the losartan-treated patients at the time of tissue biopsy.

Conclusions: Losartan treatment decreased the tissue expression of miR-21 and TGF-β and tissue fibrosis in kidney transplant patient, and it had a protective effect on allograft function and may delay chronic allograft dysfunction by reducing mediators of fibrosis.