Angiotensin II type 2 receptor (AT2R) agonist, C21, prevents the epithelial cell damage caused by renal ischemia

FUSSI M. FERNANDA; PARIANI ALEJANDRO; MOLINAS, SARA M.; HIDALGO FLORENCIA; LAROCCA, CECILIA; BUONO GABRIEL; MONASTEROLO, LILIANA A.

Santiago

Congreso; Reunión Conjunta de la Sociedad Chilena de Ciencias Fisiológicas y la Asociación Latinoamericana de Ciencias Fisiológicas (ALACF); 2020

SCHCF y ALACF

Introduction: During acute kidney injury induced by ischemia-reperfusion (IR), loss of cytoskeletal integrity and disruption ofadherent junctions are rapid events in response to ATP depletion. Angiotensin II via AT2R participates in tissue repair. Our previousdata in rats demonstrated that pretreatment with the AT2R agonist, C21, attenuated renal dysfunction caused by IR and inducedbetter preservation of tubular architecture. RhoA and Cdc42 are Rho-GTPases involved in maintenance of renal tubule epithelialintegrity. Objective: Evaluate the effects of C21 pretreatment on renal ischemia epithelial cell damage. Methodology: Male Wistarrats (n=6 per group) underwent 40 min unilateral renal ischemia + 1 day of reperfusion. C21, 0.3mg/Kg/d i.p., was administeredfor two days prior to IR. RhoA and Cdc42 protein abundance was evaluated in renal cortex by western blot. MDCK renal cells weregrown on filters in conditions that assure well-defined epithelial polarity (n=3 per group). To simulate ischemia by ATP depletion,cells were exposed to antimycin A (10 uM) and 2-deoxyglucose (10 mM) during 90 min (I). Cells were pretreated with C21 1mM(I+C21) or vehicle (C+C21) during 24 h. Cells were analyzed by immunofluorescence using Faloidin and anti E-cadherin. Data areshown as mean±SEM. Statistics: ANOVA followed by Newman-Keuls test. Institutional Animal Care Committee approved thisstudy. Results: IR downregulated cortical RhoA (-65%*) and Cdc42 (-55%*) abundance in rats. C21 prevented this decrease. InMDCK, C21 prevented the ischemia induced reduction of actin in brush border microvilli (Control (C): 44±2%; C+C21: 37±2; I:21±2*; I+C21: 45±5) and in stress fibers (C: 28±2%; C+C21: 27±4; I: 6±1*; I+C21: 23±4). Membrane E-cadherin decreased in I (-13%*) and C21 prevented this change. *p