Relationship between peroxisome proliferator-activated receptor-γ and renal ischemia-reperfusion injury

Abstract

Abstract. The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and, in particular, surface adhesion molecules, the expression of which initiates inflammatory cell attachment. It has been suggested that peroxisome proliferator-activated receptor (PPAR)-γ is an important immunomodulatory factor as well as a regulator of fatty acid. In this study, we investigated the expression of PPAR-γ in a renal I/R injury rat model. The right kidney was harvested and the left renal artery and vein were clamped by means of a laparotomy. The kidney was reperfused following 90 min of ischemia. Rats were sacrificed at 0, 1.5, 3, 5, 12 and 24 h after reperfusion. PPAR-γ expression was analyzed by immunohistochemical staining using monoclonal antibody. PPAR-γ staining was weak in the endothelial cells, interstitial cells and collecting ducts in the normal kidney. From 1.5 to 5 h after reperfusion, PPAR-γ staining was strong. Twelve hours after reperfusion, necrosis had extended throughout the kidney, and nearly all the tubular epithelial cells were destroyed. However, 12 h after reperfusion, PPAR-γ staining was weak in the endothelial cells and its expression was moderate in the interstitial cells and collecting ducts. PPAR-γ was induced in the endothelial cells, including the mesangial cells, interstitial cells and collecting ducts in a rat model of renal I/R injury. IntroductionRenal transplantation is an acceptable therapeutic approach for patients with end-stage renal disease. Renal ischemiareperfusion (I/R) injury is a clinically significant problem and an invariable consequence of renal transplantation that results from aortic cross-clamping and resuscitation after systemic hypotension. Previous studies have focused on the function of neutrophils, the action mechanisms of inflammatory cytokines, tissue factors, intercellular adhesion molecule-1, oxygen-free radicals, vascular plugging, edema and other complications (1).Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcriptional factors, which includes receptors for steroids, thyroid hormones, vitamin D 3 and retinoic acid. PPAR binds to a peroxisome proliferator responsive element to form a heterodimer with the retinoic receptor in the regulation of PPAR target genes (2).There are three known PPAR isoforms: PPAR-α, -ß and -γ. PPAR-α primarily regulates the fatty acid metabolism and has an anti-inflammatory effect; its ligands are used in fibrate drugs. PPAR-ß is ubiquitously expressed throughout the body, but its physiological functions are unknown. PPAR-γ has anti-inflammatory effects and controls the functioning of the immune system, having inhibitory action on the production of nitric oxide, cytokine and monocyte chemoattractant protein-1 and on B-cell growth, vascularization and cell growth, and differentiation-inducing action on dendritic cells and helper T-cells (3).PPAR-γ has also been implicated in inflammation and tumorigenesis (4), and significant evidenc...

Peroxisome proliferator-activated receptor γ prevents the production of NOD-like receptor family, pyrin domain containing 3 inflammasome and interleukin 1β in HK-2 renal tubular epithelial cells stimulated by monosodium urate crystals

“…PPARγ expression in cyclosporine-treated rat kidneys was significantly lower than that in the control groups (34). Matsuyama et al (35) also showed that PPARγ expression was reduced in rats following ischemia/re-perfusion. The discrepancies between these previous studies and the results of the present study may be due to differences in treatment or stimulus intensity, or due to differences between experimental in vitro and in vivo models.…”

New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

“…Similar as described for traumatic CNS injuries, a strong relationship between PPAR tissue expression and I/R injury could be demonstrated. In kidney I/R, PPAR γ expression was strongly increased in endothelial cells, interstitial cells, and collecting ducts of the kidney peaking from 1.5 to 5 hours after reperfusion [ 64 , 65 ]. Similar upregulation of PPAR γ was detected in the cortical peri-infarct area after focal cerebral ischemia in rats [ 66 ].…”