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Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice

Acute kidney injury (AKI), a critical syndrome characterized by a rapid decrease of kidney function, is a global health problem. Src family kinases (SFK) are proto-oncogenes that regulate diverse biological functions including mitochondrial function. Since mitochondrial dysfunction plays an importan...

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Autores principales: Pak, Eun Seon, Uddin, Md Jamal, Ha, Hunjoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662942/
https://www.ncbi.nlm.nih.gov/pubmed/33153232
http://dx.doi.org/10.3390/ijms21218246
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author Pak, Eun Seon
Uddin, Md Jamal
Ha, Hunjoo
author_facet Pak, Eun Seon
Uddin, Md Jamal
Ha, Hunjoo
author_sort Pak, Eun Seon
collection PubMed
description Acute kidney injury (AKI), a critical syndrome characterized by a rapid decrease of kidney function, is a global health problem. Src family kinases (SFK) are proto-oncogenes that regulate diverse biological functions including mitochondrial function. Since mitochondrial dysfunction plays an important role in the development of AKI, and since unbalanced SFK activity causes mitochondrial dysfunction, the present study examined the role of SFK in AKI. Lipopolysaccharides (LPS) inhibited mitochondrial biogenesis and upregulated the expression of NGAL, a marker of tubular epithelial cell injury, in mouse proximal tubular epithelial (mProx) cells. These alterations were prevented by PP2, a pan SFK inhibitor. Importantly, PP2 pretreatment significantly ameliorated LPS-induced loss of kidney function and injury including inflammation and oxidative stress. The attenuation of LPS-induced AKI by PP2 was accompanied by the maintenance of mitochondrial biogenesis. LPS upregulated SFK, especially Fyn and Src, in mouse kidney as well as in mProx cells. These data suggest that Fyn and Src kinases are involved in the pathogenesis of LPS-induced AKI, and that inhibition of Fyn and Src kinases may have a potential therapeutic effect, possibly via improving mitochondrial biogenesis.
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spelling pubmed-76629422020-11-14 Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice Pak, Eun Seon Uddin, Md Jamal Ha, Hunjoo Int J Mol Sci Article Acute kidney injury (AKI), a critical syndrome characterized by a rapid decrease of kidney function, is a global health problem. Src family kinases (SFK) are proto-oncogenes that regulate diverse biological functions including mitochondrial function. Since mitochondrial dysfunction plays an important role in the development of AKI, and since unbalanced SFK activity causes mitochondrial dysfunction, the present study examined the role of SFK in AKI. Lipopolysaccharides (LPS) inhibited mitochondrial biogenesis and upregulated the expression of NGAL, a marker of tubular epithelial cell injury, in mouse proximal tubular epithelial (mProx) cells. These alterations were prevented by PP2, a pan SFK inhibitor. Importantly, PP2 pretreatment significantly ameliorated LPS-induced loss of kidney function and injury including inflammation and oxidative stress. The attenuation of LPS-induced AKI by PP2 was accompanied by the maintenance of mitochondrial biogenesis. LPS upregulated SFK, especially Fyn and Src, in mouse kidney as well as in mProx cells. These data suggest that Fyn and Src kinases are involved in the pathogenesis of LPS-induced AKI, and that inhibition of Fyn and Src kinases may have a potential therapeutic effect, possibly via improving mitochondrial biogenesis. MDPI 2020-11-03 /pmc/articles/PMC7662942/ /pubmed/33153232 http://dx.doi.org/10.3390/ijms21218246 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pak, Eun Seon
Uddin, Md Jamal
Ha, Hunjoo
Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title_full Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title_fullStr Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title_full_unstemmed Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title_short Inhibition of Src Family Kinases Ameliorates LPS-Induced Acute Kidney Injury and Mitochondrial Dysfunction in Mice
title_sort inhibition of src family kinases ameliorates lps-induced acute kidney injury and mitochondrial dysfunction in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662942/
https://www.ncbi.nlm.nih.gov/pubmed/33153232
http://dx.doi.org/10.3390/ijms21218246
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