Effects of renal ischemia and Angiotensin II type 2 receptor (AT2R) agonism on end-binding protein 1 (EB1) expression

FUSSI, MARÍA F.; HIDALGO, FLORENCIA; ALEJANDRO PARIANI; RIVABELLA MAKNIS, TOMAS; GIRARDINI, JAVIER E.; MONASTEROLO, LILIANA A.; LAROCCA, M. CECILIA; MOLINAS, SARA M.

Congreso virtual

Congreso; REUNIÓN ANUAL SAFIS 2021; 2022

Sociedad Argentina de Fisiología (SAFIS)

Introduction: Ischemic injury is one of the main causes of acute kidney injury (AKI). Tubularremodeling in response to AKI involves the dedifferentiation and regeneration of theremaining epithelial tubular cells. Microtubule dynamic instability plays a central role in renalrepair after AKI. EB1 is a central regulator of microtubule dynamic instability that participatesin tubulogenesis. We demonstrated that AT2R activation by its agonist C21, preventedtubular epithelial cell damage induced by ischemic injury in a rat model and in MDCK cells.Objective: To evaluate if the renoprotective effects of C21 were associated with changes inEB1 expression.Methods: Male Wistar rats (n=6) underwent 40 min unilateral renal ischemia + 1 day ofreperfusion (IR). C21, 0.3mg/Kg/d i.p. (Vicore Pharma), was administered for two days priorto IR or sham operation. MDCK cells were grown in conditions that assure well-definedepithelial polarity (n=3).To simulate ischemia by ATP depletion, cells were exposed toantimycin A (10 uM) and 2-deoxyglucose (10 mM) during 90 min followed by 24 hreoxigenation. Cells were pretreated with C21 1mM or its vehicle during 24 h. EB1 proteinabundance was evaluated in renal cortex or in MDCK lysates by western blot. Data areexpressed as mean±SEM. Statistics: ANOVA followed by Newman-Keuls test.Results: In rats, IR damage reduced EB1 expression (-50%*). C21 increased EB1expression in sham (+230%*) and IR (+83%*,#) animals. Similarly, MDCK cells submitted toIR showed a decrease in EB1 expression (-72%*) that was partially prevented by C21(-25%*,#). C21 increased EB1 expression in control (+45%*). *p 0.05 vs C, #p