title: Epigenetic changes and alteration of Fbn1 and Col3A1 gene expression under hyperglycaemic and hyperinsulinaemic conditions.
abstract: Little is known regarding the role of hyperglycaemia on histone H3 modifications and, in turn, altering the expression of genes during the development of diabetes-associated complications. In the present study, we have investigated the hyperinsulinaemia/hyperglycaemia-induced epigenetic changes and alteration of Fbn1 (fibrillin 1) and Col3A1 (collagen type III α1) gene expression. Insulin resistance and Type 2 diabetes in male Sprague-Dawley rats was developed by feeding rats an HFD (high-fat diet) and administering a low dose of STZ (streptozotocin). Hyperglycaemia induced deacetylation and dephosphorylation of histone H3 in the heart and kidneys of diabetic rats. Furthermore, mRNA expression of Fbn1 and Col3A1 increased in the kidneys and decreased in the heart under hyperglycaemic/hyperinsulinaemic conditions. Similar to mRNA expression, chromatin immunoprecipitation also showed an increase in the level of histone H3 acetylation of the Fbn1 gene, but not of the Col3A1 gene. Our present findings suggests that the change in expression of the Fbn1 gene is epigenetically regulated, but the expression of the Col3A1 gene may either be independent of epigenetic regulation or may involve other histone modifications. We provide the first evidence regarding the role of hyperglycaemia/hyperinsulinaemia in altering histone H3 modifications, which may result in the alteration of extracellular matrix gene expression.
authors.affiliation: Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab-160 062, India.
authors.forename: Anil B
authors.initials: AB
authors.lastname: Gaikwad
authors.forename: Jeena
authors.initials: J
authors.lastname: Gupta
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
mesh_terms: D000818:Animals; D024061:Collagen Type III / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology; D003925:Diabetic Angiopathies / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000473:pathology; D003929:Diabetic Neuropathies / Q000235:genetics / Q000473:pathology; D000071838:Fibrillin-1; D000071837:Fibrillins; D005786:Gene Expression Regulation; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D006946:Hyperinsulinism / Q000235:genetics*; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics; D007668:Kidney / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054392:Adipokines
chemical_list: D024061:Collagen Type III; D000071838:Fibrillin-1; D000071837:Fibrillins; D006657:Histones; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605725:Fbn1 protein, rat