A genome-wide screen reveals microRNAs in peripheral sensory neurons driving painful diabetic neuropathy.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
received:
10
06
2020
accepted:
23
11
2020
pubmed:
26
1
2021
medline:
20
5
2021
entrez:
25
1
2021
Statut:
ppublish
Résumé
Diabetes is a leading cause of peripheral neuropathy (diabetic peripheral neuropathy, DPN), and uncontrolled long-lasting hyperglycemia leads to severe complications. A major proportion of diabetics develop excruciating pain with a variable course. Mechanisms leading to painful DPN are not completely understood and treatment options limited. We hypothesized that epigenetic modulation at the level of microRNA (miRNA) expression triggered by metabolic imbalance and nerve damage regulates the course of pain development. We used clinically relevant preclinical models, genome-wide screening, in silico analyses, cellular assays, miRNA fluorescent in situ hybridization, in vivo molecular manipulations, and behavioral analyses in the current study. We identified miRNAs and their targets that critically impact on nociceptive hypersensitivity in painful DPN. Our analyses identify miR-33 and miR-380 expressed in nociceptive neurons as critical denominators of diabetic pain and miR-124-1 as a mediator of physiological nociception. Our comprehensive analyses on the putative mRNA targets for miR-33 or miR-124-1 identified a set of mRNAs that are regulated after miR-33 or miR-124-1 overexpression in dorsal root ganglia in vivo. Our results shed light on the regulation of DPN pathophysiology and implicate specific miRNAs as novel therapeutic targets for treating painful DPN.
Identifiants
pubmed: 33492037
doi: 10.1097/j.pain.0000000000002159
pii: 00006396-202105000-00007
doi:
Substances chimiques
MIRN380 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1334-1351Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 International Association for the Study of Pain.
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