Producción CyT

PANAM Physiological Sciences 2023 Abstract Book - Mechanistic insight into angiotensin II type 2 receptor (AT2R) nephroprotective effect during renal ischemia/reperfusion

Congreso

Autoría:

Rivabella Matkins Tomas ; Fussi M. Fernanda ; Pariani Alejandro ; Huhn Victoria ; Favre Cristian ; MOLINAS, SARA MARIA ; Larocca, M. Cecilia

Fecha:

2023

Editorial y Lugar de Edición:

Asociación Latinoamericana de Ciencias Fisiológicas

Resumen *

Introduction: AT2R agonist C21 elicits nephroprotective effects in ischemia/reperfusion (IR)-induced acute kidney injury (AKI) by preventing tubular cell damage. IR-induced AKI is associated with tubular cell deciliation. Primary cilia are sensory organelles, whose stability depends on α-tubulin acetylation. Extracellular signalregulated kinases (ERK) activate α-tubulin deacetylase HDAC6.Objective: To get mechanistic insight for C21 nephroprotective effect during IR.Methods: Male Wistar rats were pretreated 24h with C21 0,3 mg/kg/day and subjected tounilateral renal IR (n=3-5 rats/group; Institutional Animal Care and Use Committee- FBIOyF Resolution #023-2020). C21 effect was also assessed using a serum/ATP depletion model of IR in MDCK cells (n=3-4 independent experiments). C21 or MEK1/2 inhibitors (PD98059 5μM or U0126 10μM) were added to the media 24h before IR. Cell ciliation, relative cilia levels of acetylated-α- tubulin (c-Ac-αtub) and ERK1/2 localization were analyzed by immunofluorescence microscopy, activated ERK (pERK) by immunoblotting and cell viability by Trypan blue exclusion test. For cilia length, results are expressed as media±S.E.M. ANOVA/Holm-Sidak-test, Kruskal- Wallis/Dunn’s-test or t-test were applied. *p<0.05 vs control (C), #p<0.05 vs C-IR.Results: C21 prevented IR-induced cilia shortening (length (um): C:3.7+/-0.3; C21:3.4+/-0.3; C-IR:2.1+/-0.1*; C21-IR:2.9+/- 0.3) and cell deciliation (C-IR:-32%*; C21-IR:- 14%#) and increased basal c-Ac-αtub (+38%*) in renal proximal tubules in the rat. C21 also increased c-Ac-αtub in MDCK cells(+34%*), whereas it inhibited ERK1/2 activation (pERK1:-30%*; pERK2:- 34%*).ERK1/2 was conspicuously localized at the primary cilia.ERK1/2 inhibitors partially prevented IR-induced decrease in cell viability (C-IR:-34%*,U0126-IR:-19%*#; C-IR:- 22%*, PD98059-IR:-14%*#), and increased basal c-Ac-αtub (U0126:+22%*; PD98059:+20%*).Conclusions: AT2R nephroprotective effect is associated with primary cilia stabilization byinhibition of the ERK1/2 pathway. Información suministrada por el agente en SIGEVA

Palabras Clave

ANGIOTENSIN II TYPE 2 RECPETORISCHEMIA REPERFUSION INJURYKIDNEY