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

FUSSI M. FERNANDA; FLORENCIA, HIDALGO; RIVABELLA MATKINS TOMAS; GIRARDINI JAVIER; LILIANA A. MONASTEROLO; LAROCCA, CECILIA; MOLINAS, SARA M.

Virtual

Congreso; SAFIS + ALACF 2021joint meeting; 2021

Sociedad Argentina de Fisiología y Asociación Latinoamericana de Ciencias Fisiológicas

Introduction: Ischemic injury is one of the main causes of acute kidney injury (AKI). Tubular remodeling in response to AKI involves the dedifferentiation and regeneration of the remaining epithelial tubular cells. Microtubule dynamic instability plays a central role in renal repair after AKI. EB1 is a central regulator of microtubule dynamic instability that participates in tubulogenesis. We demonstrated that AT2R activation by its agonist C21, prevented tubular 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 in EB1 expression. Methods: Male Wistar rats (n=6) underwent 40 min unilateral renal ischemia + 1 day of reperfusion (IR). C21, 0.3mg/Kg/d i.p. (Vicore Pharma), was administered for two days prior to IR or sham operation. MDCK cells were grown in conditions that assure well-defined epithelial polarity (n=3).Tosimulate ischemia by ATP depletion, cells were exposed to antimycin A (10 uM) and 2-deoxyglucose (10 mM) during 90 min followed by 24 h reoxigenation. Cells were pretreated with C21 1mM or its vehicle during 24 h. EB1 protein abundance was evaluated in renal cortexor in MDCK lysates by western blot. Data are expressed as mean±SEM. Statistics: ANOVA followed by Newman-Keuls test. Results: In rats, IR damage reduced EB1 expression (-50%*). C21 increased EB1 expression in sham (+230%*) and IR (+83%*,#) animals. Similarly, MDCK cells submitted to IR 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