PMID- 37771329
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231003
IS  - 1948-9358 (Print)
IS  - 1948-9358 (Electronic)
IS  - 1948-9358 (Linking)
VI  - 14
IP  - 9
DP  - 2023 Sep 15
TI  - MicroRNA-155 mediates endogenous angiotensin II type 1 receptor regulation: 
      implications for innovative type 2 diabetes mellitus management.
PG  - 1334-1340
LID - 10.4239/wjd.v14.i9.1334 [doi]
AB  - 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/EBPbeta, HDAC4, 
      and SOCS1 impacts insulin signaling, deteriorating glucose homeostasis, and 
      causing insulin resistance (IR). Moreover, deranged regulation of the renin 
      angiotensin aldo-sterone 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-inflammatory cellular pathways, and promotes beta-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.
CI  - (c)The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Papadopoulos, Konstantinos I
AU  - Papadopoulos KI
AD  - Department of R&D, THAI StemLife, Bangkok 10310, Thailand. 
      kostas@thaistemlife.co.th.
FAU - Papadopoulou, Alexandra
AU  - Papadopoulou A
AD  - Occupational and Environmental Health Services, Feelgood Lund, Lund 223-63, 
      Skane, Sweden.
FAU - Aw, Tar-Choon
AU  - Aw TC
AD  - Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, 
      Singapore, Singapore.
AD  - Department of Medicine, National University of Singapore, Singapore 119228, 
      Singapore, Singapore.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - World J Diabetes
JT  - World journal of diabetes
JID - 101547524
PMC - PMC10523232
OTO - NOTNLM
OT  - Angiotensin II
OT  - Angiotensin II type 1 receptor
OT  - Arginase 2
OT  - L-type calcium channel
OT  - MiRNA-155
OT  - Mineralocorticoid receptor
OT  - Renin-angiotensin aldosterone system
OT  - Type 1/2 diabetes mellitus
OT  - Verapamil
COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of 
      interest for this article.
EDAT- 2023/09/29 06:44
MHDA- 2023/09/29 06:45
PMCR- 2023/09/15
CRDT- 2023/09/29 03:44
PHST- 2023/04/14 00:00 [received]
PHST- 2023/06/18 00:00 [revised]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/09/29 06:45 [medline]
PHST- 2023/09/29 06:44 [pubmed]
PHST- 2023/09/29 03:44 [entrez]
PHST- 2023/09/15 00:00 [pmc-release]
AID - 10.4239/wjd.v14.i9.1334 [doi]
PST - ppublish
SO  - World J Diabetes. 2023 Sep 15;14(9):1334-1340. doi: 10.4239/wjd.v14.i9.1334.