MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation:implications for innovative type 2 diabetes mellitus management  

作　　者：Konstantinos I Papadopoulos Alexandra Papadopoulou Tar-Choon Aw 

机构地区：[1]Department of R&D,THAI StemLife,Bangkok 10310,Thailand [2]Occupational and Environmental Health Services,Feelgood Lund,Lund 223-63,Skåne,Sweden [3]Department of Laboratory Medicine,Changi General Hospital,Singapore 529889,Singapore,Singapore [4]Department of Medicine,National University of Singapore,Singapore 119228,Singapore,Singapore

出　　处：《World Journal of Diabetes》2023年第9期1334-1340,共7页世界糖尿病杂志（英文版）（电子版）

摘　　要：Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharmacological interventions.MicroRNAs(miRNA),are small,non-coding,one-stranded RNA molecules,that can target and silence around 60%of all human genes through translational repression.MiR-155 is an ancient,evolutionarily well-conserved miRNA,with distinct expression profiles and multifunctionality,and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation,immunity,inflammation,viral infections,cancer,cardiovascular conditions,and particularly diabetes mellitus.MiR-155 Levels are progressively reduced in aging,obesity,sarcopenia,and T2DM.Thus,the loss of coordinated repression of multiple miR-155 targets acting as negative regulators,such as C/EBPβ,HDAC4,and SOCS1 impacts insulin signaling,deteriorating glucose homeostasis,and causing insulin resistance(IR).Moreover,deranged regulation of the renin angiotensin aldosterone system(RAAS)through loss of Angiotensin II Type 1 receptor downregulation,and negated repression of ETS-1,results in unopposed detrimental Angiotensin II effects,further promoting IR.Finally,loss of BACH1 and SOCS1 repression abolishes cytoprotective,anti-oxidant,anti-apoptotic,and anti-inflam matory cellular pathways,and promotesβ-cell loss.In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels,strategies to increase an ailing miR-155 production in T2DM,e.g.,the use of metformin,mineralocorticoid receptor blockers(spironolactone,eplerenone,finerenone),and verapamil,alone or in various combinations,represent current treatment options.In the future,direct tissue delivery of miRNA analogs is likely.

关 键 词：Angiotensin II Angiotensin II type 1 receptor Arginase 2 L-type calcium channel Mineralocorticoid receptor MiRNA-155 Renin-angiotensin aldosterone system Type 1/2 diabetes mellitus VERAPAMIL 

分 类 号：R587.2[医药卫生—内分泌]