Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury
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 injur...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/4609502 |
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| author | Shataakshi Dube Tejasvi Matam Jessica Yen Henry E. Mang Pierre C. Dagher Takashi Hato Timothy A. Sutton |
| author_facet | Shataakshi Dube Tejasvi Matam Jessica Yen Henry E. Mang Pierre C. Dagher Takashi Hato Timothy A. Sutton |
| author_sort | Shataakshi Dube |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a6b0f66e3f294dc18ff8e32f828822b3 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-a6b0f66e3f294dc18ff8e32f828822b32025-02-03T01:11:53ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/46095024609502Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney InjuryShataakshi Dube0Tejasvi Matam1Jessica Yen2Henry E. Mang3Pierre C. Dagher4Takashi Hato5Timothy A. Sutton6Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USASTAT3 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.http://dx.doi.org/10.1155/2017/4609502 |
| spellingShingle | Shataakshi Dube Tejasvi Matam Jessica Yen Henry E. Mang Pierre C. Dagher Takashi Hato Timothy A. Sutton Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury Journal of Immunology Research |
| title | Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury |
| title_full | Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury |
| title_fullStr | Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury |
| title_full_unstemmed | Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury |
| title_short | Endothelial STAT3 Modulates Protective Mechanisms in a Mouse Ischemia-Reperfusion Model of Acute Kidney Injury |
| title_sort | endothelial stat3 modulates protective mechanisms in a mouse ischemia reperfusion model of acute kidney injury |
| url | http://dx.doi.org/10.1155/2017/4609502 |
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