Semaphorin 3A Inactivation Suppresses Ischemia-reperfusion-induced Inflammation and Acute Kidney Injury

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2014 May 16

PMID 24829504

Citations 23

Authors

Punithavathi Ranganathan

Calpurnia Jayakumar

Riyaz Mohamed

Neal L Weintraub

Ganesan Ramesh

Affiliations

Soon will be listed here.

Abstract

Recent studies show that guidance molecules that are known to regulate cell migration during development may also play an important role in adult pathophysiologic states. One such molecule, semaphorin3A (sema3A), is highly expressed after acute kidney injury (AKI) in mice and humans, but its pathophysiological role is unknown. Genetic inactivation of sema3A protected mice from ischemia-reperfusion-induced AKI, improved tissue histology, reduced neutrophil infiltration, prevented epithelial cell apoptosis, and increased cytokine and chemokine excretion in urine. Pharmacological-based inhibition of sema3A receptor binding likewise protected against ischemia-reperfusion-induced AKI. In vitro, sema3A enhanced toll-like receptor 4-mediated inflammation in epithelial cells, macrophages, and dendritic cells. Moreover, administration of sema3A-treated, bone marrow-derived dendritic cells exacerbated kidney injury. Finally, sema3A augmented cisplatin-induced apoptosis in kidney epithelial cells in vitro via expression of DFFA-like effector a (cidea). Our data suggest that the guidance molecule sema3A exacerbates AKI via promoting inflammation and epithelial cell apoptosis.

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