Renal progenitor cells modulated by angiotensin II receptor blocker (ARB) medication and differentiation towards podocytes in anti-thy1.1 nephritis.

Abstract

BackgroundMesangial proliferative glomerulonephritis (MsPGN) is an epidemic disease with increasing occurrence. As important as mesangial cells, podocytes are key innate cells for MsPGN prognosis and recovery. Renal progenitor cells, located at the urinary pole (UP) of Bowman’s capsule (BC), could alleviate kidney injury through their capacity to differentiate into podocytes.MethodsSeventy-two male rats were categorized randomly into the sham (n=24), untreated Thy-1 (n=24) and losartan-treated (n=24) groups. We administered vehicle or losartan (50 mg/kg by gavage) daily to treat rats with anti-thy1.1 nephritis, an ideal model to simulate human MsPGN. Two weeks after the intravenous injection of antibody, urinary protein and blood samples were analyzed, pathological changes were examined, the number of podocytes was determined, and renal progenitor cells were studied.ResultsAnti-thy1.1 nephritis was significantly alleviated after losartan treatment, as reported previously and as expected. Compared with the untreated Thy-1 group, the number of podocytes in the losartan group increased, and the area of renal progenitor cells significantly increased. The protein expression of components of the p-ERK pathway was determined during the development of renal progenitor cells differentiating into podocytes.ConclusionsThe data in this paper show the direct glomerular cell action of angiotensin II receptor blocker (ARB) treatment in improving outcomes in anti-thy1.1 nephritis. The positive effects of ARB medication on anti-thy1.1 nephritis were due to an increase in the number of renal epithelial progenitor cells (defined as PECs that expressed only stem cell markers without podocyte proteins).