Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury

Shataakshi Dube, Tejasvi Matam, Jessica Yen, Henry E. Mang, Pierre Dagher, Takashi Hato, Timothy Sutton

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

STAT3 is a transcriptional regulator that plays an important role in coordinating inflammation and immunity. In addition, there is a growing appreciation of the role STAT3 signaling plays in response to organ injury following diverse insults. Acute kidney injury (AKI) from ischemia-reperfusion injury is a common clinical entity with devastating consequences, and the recognition that endothelial alterations contribute to kidney dysfunction in this setting is of growing interest. Consequently, we used a mouse with a genetic deletion of Stat3 restricted to the endothelium to examine the role of STAT3 signaling in the pathophysiology of ischemic AKI. In a mouse model of ischemic AKI, the loss of endothelial STAT3 signaling significantly exacerbated kidney dysfunction, morphologic injury, and proximal tubular oxidative stress. The increased severity of ischemic AKI was associated with more robust endothelial-leukocyte adhesion and increased tissue accumulation of F4/80+ macrophages. Moreover, important proximal tubular adaptive mechanisms to injury were diminished in association with decreased tissue mRNA levels of the epithelial cell survival cytokine IL-22. In aggregate, these findings suggest that the endothelial STAT3 signaling plays an important role in limiting kidney dysfunction in ischemic AKI and that selective pharmacologic activation of endothelial STAT3 signaling could serve as a potential therapeutic target.

Original languageEnglish (US)
Article number4609502
JournalJournal of Immunology Research
Volume2017
DOIs
StatePublished - Jan 1 2017

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Acute Kidney Injury
Reperfusion
Ischemia
Kidney
Wounds and Injuries
Tissue Adhesions
Reperfusion Injury
Endothelium
Immunity
Cell Survival
Oxidative Stress
Leukocytes
Epithelial Cells
Macrophages
Cytokines
Inflammation
Messenger RNA
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury. / Dube, Shataakshi; Matam, Tejasvi; Yen, Jessica; Mang, Henry E.; Dagher, Pierre; Hato, Takashi; Sutton, Timothy.

In: Journal of Immunology Research, Vol. 2017, 4609502, 01.01.2017.

Research output: Contribution to journalArticle

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