RhoGTPases and end-binding protein 1 (EB1) expression associated with apelin-induced proximal tubule function improvement in the postischemic kidney

MOLINAS, SARA M.; HIDALGO FLORENCIA; BARSI FLORENCIA ; TABORRA M. EUGENIA ; RIVABELLA MATKINS TOMAS; GIRARDINI JAVIER; LAROCCA, CECILIA; MONASTEROLO, LILIANA A.

Rosario

Congreso; Congreso de la Sociedad Argentina de Fisiología 2019; 2019

Sociedad Argentina de Fisiología

Understanding the mechanisms of kidney repair after ischemic injury is critical in the research of new therapeutic strategies. The repair process is accomplished by migration of new cells into the region, reconstituting the functional tubular epithelium. Ischemia?reperfusion induces changes in expression and distribution of Rho GTPases in proximal tubules. Similarly to Rho GTPases, EB1 is an important regulator of microtubule and actin dynamics, essential for kidney tubular cell-migration and epithelial remodelling. Furthermore, in certain scenarios, EB1 regulatory function overlaps with Rho GTPases signalling. Increasing evidence indicates that the adipokine apelin and its receptor, APJ, may be potential target for the treatment of kidney disease. The aim of this study was to evaluate the effects of apelin on functional parameters and the expression of RhoGTPases and EB1 in the post-ischemic kidney. Male Wistar rats (n= 4 per group) underwent 40 min unilateral renal ischemia followed by 24 h reperfusion (IR) or sham surgery (C). Apelin 50ug/Kg/d i.p. was administered during 3 days prior to IR (IR+Ap). Increased fractional glucose excretion in IR was prevented by Ap treatment (C: 0.0042 +/- 0.001%; IR: 0.25 +/- 0.06*; IR+Ap: 0.0097 +/- 0.004#). Western blot analysis of cortical plasma membrane fractions showed diminished levels of the RhoGTPases Cdc42 (C: 1 +/- 0.24; IR: 0.19 +/- 0.02*; IR+Ap: 0.64 +/- 0.10#) and RhoA (C: 1 +/- 0.19; IR: 0.11 +/- 0.05*; IR+Ap: 0.43 +/- 0.18#; *p