Role of Epigenetics in Modulating Inflammatory Response Mediated by NF and#954;B through AT1 or AT2 receptors in the Development of Renal Failure under Type 2 Diabetic Condition

Abstract

Type 2 diabetes induced nephropathy, one of the major causes of end newlinestage renal failure globally has been known to be associated with severe newlinehemodynamic imbalance which in turn activates renin angiotensin system (RAS). newlineAngiotensin II (Ang II) is the most potent component responsible for widespread newlinebiological actions by acting majorly through Ang II type 1 receptors (AT1) and Ang II newlinetype 2 receptors (AT2). Though a vast scale of studies have been performed regarding newlinethe role of AT1 receptor inhibition in treatment of diabetic nephropathy and its role in newlinecontrolling nuclear factor and#954;B (NF-and#954;B) mediated inflammatory cascade, the view newlineregarding the role of AT2 receptors in regulation of NF-and#954;B signaling remained newlinemystified. Existing studies showed that NF-and#954;B signaling was regulated by different newlineAng II receptor sub-types in different tissues and conditions, thereby urging us to newlinedetermine the exact roles of Ang II receptor sub-types in regulation of this pathway in newlinediabetic nephropathy. Also the effect of AT1 and AT2 receptors activity on newlineexpression of Angiotensin Converting Enzyme (ACE) and Angiotensin Converting newlineEnzyme 2 (ACE2) remained unknown, despite their significant roles as components newlineof deteriorative and protective axes of RAS. Another important gap in the existing newlineliterature was that though angiotensin receptor blockers and ACE inhibitors are the newlinemainstay of currently available pharmacological interventions, their effects on newlineepigenetic modifications have not been studied in-depth. As suggested by the recent newlinestudies, genetic penchant alone may not be sufficient to explain the pathogenesis of newlinediabetic nephropathy and thus, epigenetic mechanisms must be studied thoroughly to newlineunderstand the complete phenomenon. Posttranslational histone modifications, newlineinvolving covalent modifications of histones play a substantial role in regulation of newlinegene transcription and are extremely important to unearth the exact pathogenic basis newlineof diabetic nephropathy as well as its treatments. Hence, in the current study we newlineaimed to check t