INVESTIGADORES
MOLINAS Sara Maria
congresos y reuniones científicas
Título:
Angiotensin II type 2 receptor (AT2R) agonist, C21, prevents the epithelial cell damage caused by renal ischemia
Autor/es:
FUSSI M. FERNANDA; HIDALGO FLORENCIA; BUONO GABRIEL; PARIANI ALEJANDRO; LAROCCA, CECILIA; MONASTEROLO, LILIANA A.; MOLINAS, SARA M.
Lugar:
Santiago
Reunión:
Congreso; Congreso de la Asociación Latinoamericana de Ciencias Fisiológicas 2020; 2020
Institución organizadora:
SCHCF y ALACF
Resumen:
Introduction: During acute kidney injury induced by ischemia-reperfusion (IR), loss of cytoskeletal integrity and disruption of adherent junctions are rapid events in response to ATP depletion. Angiotensin II via AT2R participates in tissue repair. Our previous data in rats demonstrated that pretreatment with the AT2R agonist, C21, attenuated renal dysfunction caused by IR and induced better preservation of tubular architecture. RhoA and Cdc42 are Rho-GTPases involved in maintenance of renal tubule epithelial integrity. Objective: Evaluate the effects of C21 pretreatment on renal ischemia epithelial cell damage. Methodology: Male Wistar rats (n=6 per group) underwent 40 min unilateral renal ischemia + 1 day of reperfusion. C21, 0.3mg/Kg/d i.p., was administered for two days prior to IR. RhoA and Cdc42 protein abundance was evaluated in renal cortex by western blot. MDCK renal cells were grown 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 are shown as mean±SEM. Statistics: ANOVA followed by Newman-Keuls test. Institutional Animal Care Committee approved this study. Results: IR downregulated cortical RhoA (-65%*) and Cdc42 (-55%*) abundance in rats. C21 prevented this decrease. In MDCK, 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