Semaphorin 3A inactivation suppresses ischemia-reperfusion-induced inflammation and acute kidney injury

Punithavathi Ranganathan, Calpurnia Jayakumar, Riyaz Mohamed, Neal L. Weintraub, Ganesan Ramesh

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)F183-F194
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2014

Fingerprint

Semaphorin-3A
Acute Kidney Injury
Reperfusion
Ischemia
Epithelial Cells
Inflammation
Apoptosis
Dendritic Cells
Kidney
Toll-Like Receptor 4
Neutrophil Infiltration
Chemokines
Cisplatin
Cell Movement
Histology
Bone Marrow
Macrophages
Urine
Pharmacology
Cytokines

Keywords

  • Acute kidney injury
  • Cisplatin
  • Semaphorin3A

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Semaphorin 3A inactivation suppresses ischemia-reperfusion-induced inflammation and acute kidney injury. / Ranganathan, Punithavathi; Jayakumar, Calpurnia; Mohamed, Riyaz; Weintraub, Neal L.; Ramesh, Ganesan.

In: American Journal of Physiology - Renal Physiology, Vol. 307, No. 2, 15.07.2014, p. F183-F194.

Research output: Contribution to journalArticle

Ranganathan, Punithavathi ; Jayakumar, Calpurnia ; Mohamed, Riyaz ; Weintraub, Neal L. ; Ramesh, Ganesan. / Semaphorin 3A inactivation suppresses ischemia-reperfusion-induced inflammation and acute kidney injury. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 307, No. 2. pp. F183-F194.
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