Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury

INTRODUCTION: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has...

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Autores principales: Li, Han, Xu, Jun-Xian, Cheng, Tiao-Chun, Tian, Li-Jun, Lin, Jin-Feng, Luo, Xi, Bian, Zhao-Lian, Han, Xu-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808661/
https://www.ncbi.nlm.nih.gov/pubmed/36130530
http://dx.doi.org/10.1159/000526916
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author Li, Han
Xu, Jun-Xian
Cheng, Tiao-Chun
Tian, Li-Jun
Lin, Jin-Feng
Luo, Xi
Bian, Zhao-Lian
Han, Xu-Dong
author_facet Li, Han
Xu, Jun-Xian
Cheng, Tiao-Chun
Tian, Li-Jun
Lin, Jin-Feng
Luo, Xi
Bian, Zhao-Lian
Han, Xu-Dong
author_sort Li, Han
collection PubMed
description INTRODUCTION: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI. METHODS: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated. RESULTS: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway. CONCLUSIONS: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury.
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spelling pubmed-98086612023-01-04 Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury Li, Han Xu, Jun-Xian Cheng, Tiao-Chun Tian, Li-Jun Lin, Jin-Feng Luo, Xi Bian, Zhao-Lian Han, Xu-Dong Kidney Blood Press Res Research Article INTRODUCTION: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI. METHODS: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated. RESULTS: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway. CONCLUSIONS: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury. S. Karger AG 2022-09-21 /pmc/articles/PMC9808661/ /pubmed/36130530 http://dx.doi.org/10.1159/000526916 Text en Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.
spellingShingle Research Article
Li, Han
Xu, Jun-Xian
Cheng, Tiao-Chun
Tian, Li-Jun
Lin, Jin-Feng
Luo, Xi
Bian, Zhao-Lian
Han, Xu-Dong
Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title_full Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title_fullStr Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title_full_unstemmed Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title_short Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury
title_sort inhibition of phosphoinositide 3-kinase gamma protects endothelial cells via the akt signaling pathway in sepsis-induced acute kidney injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808661/
https://www.ncbi.nlm.nih.gov/pubmed/36130530
http://dx.doi.org/10.1159/000526916
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