Pioglitazone modulates immune activation and ameliorates inflammation induced by injured renal tubular epithelial cells via PPAR[gamma]/miRNA-124/STAT3 signaling

Acute kidney injury (AKI) is commonly a result of renal ischemia reperfusion injury (IRI), which produces clinical complications characterized by the rapid deterioration of renal function, leading to chronic kidney disease and increases the risk of morbidity and mortality. Currently, only supportive...

Full description

Saved in:
Bibliographic Details
Published inBiomedical reports Vol. 18; no. 1; p. 1
Main Authors Gazzar, Walaa Bayoumie El, Allam, Mona Maher, Shaltout, Sherif Ahmed, Mohammed, Lina Abdelhady, Sadek, Ashraf Mohamed, Nasr, Hend Elsayed
Format Journal Article
LanguageEnglish
Published Spandidos Publications 01.01.2023
Subjects
Antigens
Chronic kidney failure
Complications and side effects
Enzyme-linked immunosorbent assay
Inflammation
Ischemia
MicroRNA
Nitric oxide
Penicillin G procaine
Egypt
Online AccessGet full text

Cover

More Information
Summary:Acute kidney injury (AKI) is commonly a result of renal ischemia reperfusion injury (IRI), which produces clinical complications characterized by the rapid deterioration of renal function, leading to chronic kidney disease and increases the risk of morbidity and mortality. Currently, only supportive treatment is available. AKI, which is accompanied by immune activation and inflammation, is caused by proximal tubular injury. The present study investigated the role of tubular epithelial cells as drivers of inflammation in renal IRI and their potential function as antigen-presenting cells, as well as the molecular mechanisms by which peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) agonists [such as pioglitazone (Pio)] exert reno-protective action in renal IRI. A total of 50 Wistar male albino rats were divided into five groups: Sham + DMSO, Sham + Pio, IRI + DMSO, IRI + prophylactic preoperative (pre) Pio and IRI + postoperative Pio. The histopathological changes in renal tissue samples and the renal epithelial cell expression of CD86, miRNA-124, STAT3, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and Arginase-II were analyzed by immunohistochemistry, reverse transcription-quantitative PCR, western blotting and ELISA respectively. IRI was a potent inducer for CD86 immunoexpression. An ameliorative action of Pio was demonstrated via decreased CD86 immunoexpression, upregulation of miRNA-124, decreased STAT3 expression and beneficial anti-inflammatory effects. The tubular epithelium served a notable role in the inflammatory response in renal IRI. Pio exerted its anti-inflammatory effects via PPAR[gamma]/miRNA-124/STAT3 signaling. Key words: peroxisome proliferator-activated receptor-y, pioglitazone, renal ischemia reperfusion injury, microRNA-124, STAT3
ISSN:2049-9434
2049-9442
DOI:10.3892/br.2022.1584