Inhibition of src family kinases ameliorates lps-induced acute kidney injury and mitochondrial dysfunction in mice

Eun Seon Pak, Md Jamal Uddin, Hunjoo Ha

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Article number8246
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume21
Issue number21
DOIs
StatePublished - 1 Nov 2020

Keywords

  • Acute kidney injury
  • Inflammation
  • Mitochondrial biogenesis
  • Oxidative stress
  • Src family kinases inhibitor

Fingerprint

Dive into the research topics of 'Inhibition of src family kinases ameliorates lps-induced acute kidney injury and mitochondrial dysfunction in mice'. Together they form a unique fingerprint.

Cite this