Published online Nov 6, 2015. doi: 10.4292/wjgpt.v6.i4.120
Peer-review started: April 18, 2015
First decision: June 18, 2015
Revised: July 11, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: November 6, 2015
Processing time: 211 Days and 2.4 Hours
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identified so far. PPARα is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPARβ/δ is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPARα or PPARγ target genes. PPARγ1 and γ2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPARγ1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPARα agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPARα agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPARγ activators. In all the studies, both the PPARγ activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARα and PPARγ may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs α and γ in gastric ulcer.
Core tip: Peroxisome proliferator-activated receptors (PPARs) are a nuclear hormone receptor family and act as transcription factors. PPARs are of three subtypes, i.e., PPARα, PPARβ/δ, and PPARγ. The common sites where PPARα is expressed are muscle, heart, liver, small intestine and kidney. PPARγ is involved in modulation of various functions like inflammation, cell proliferation, and differentiation and it is commonly expressed in white blood cells (e.g., macrophages and monocytes) which are involved in immune activity and in the colon. Studies in animals have demonstrated the gastric antisecretory activity of PPARα agonists like ciprofibrate, bezafibrate and clofibrate. The majority of the experimental studies regarding the role of PPARγ activators is on pioglitazone and rosiglitazone. In all the studies, both the PPARγ activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARα and PPARγ can be explored as a target of gastric ulcer treatment. The aim of the present paper is to discuss the experimental evidences of the role of PPARs in gastric ulcer.