Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγ in epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγ ligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγ in the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy.
Highlights
The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor highly expressed in adipose tissue and intestine, playing a key role in regulation of insulin resistance and inflammation
The inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis (UC) are common causes of gastrointestinal illness characterised by chronic, relapsing intestinal inflammation, often presenting in early childhood [1]
To date there are 99 IBD susceptibility loci: 71 associated with Crohn’s disease, 47 with ulcerative colitis, and 28 with both CD and UC [5, 6]. Amongst these are multiple genes involved in IL23/Th17 signaling (IL23R, IL12B, JAK2, TYK2, and STAT3), genes involved in autophagy, intracellular bacteria processing and innate immunity (NOD2, IRGM, and ATG16L1), and genes involved in barrier (HNF4A, LAMB1, CDH1, and GNA1e)
Summary
The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor highly expressed in adipose tissue and intestine, playing a key role in regulation of insulin resistance and inflammation. Its role in intestinal diseases, especially colon cancer and intestinal inflammation, is emerging. The discovery that it is the major functional receptor mediating the aminosalicylate activities in inflammatory bowel diseases (IBD) has further enhanced the interest for the role of this receptor in the regulation of gut homeostasis, with possible implication for newer therapeutic targeting. After an extensive search of medical literature in English language from the PubMed database, we aim in this paper to focus on potential role of PPARγ in the predisposition and physiopathology of IBD and to analyze its role in experimental colitis and potential therapy for IBD
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