Regulatory role of miR-146a in corneal epithelial wound healing via its inflammatory targets in human diabetic cornea.
Chemokines
Cytokines
Diabetic cornea
Limbal stem cells
NF-κB inflammatory pathway
Wound healing
miR-146a
microRNA
Journal
The ocular surface
ISSN: 1937-5913
Titre abrégé: Ocul Surf
Pays: United States
ID NLM: 101156063
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
01
11
2021
revised:
03
06
2022
accepted:
06
06
2022
pubmed:
12
6
2022
medline:
10
8
2022
entrez:
11
6
2022
Statut:
ppublish
Résumé
MiR-146a upregulated in limbus vs. central cornea and in diabetic vs. non-diabetic limbus has emerged as an important immune and inflammatory signaling mediator in corneal epithelial wound healing. Our aim was to investigate the potential inflammation-related miR-146a target genes and their roles in normal and impaired diabetic corneal epithelial wound healing. Our previous data from RNA-seq combined with quantitative proteomics of limbal epithelial cells (LECs) transfected with miR-146a mimic vs. mimic control were analyzed. Western blot and immunostaining were used to confirm the expression of miR-146a inflammatory target proteins in LECs and organ-cultured corneas. Luminex assay was performed on conditioned media at 6- and 20-h post-wounding in miR-146a mimic/inhibitor transfected normal and diabetic cultured LECs. Overexpression of miR-146a decreased the expression of pro-inflammatory TRAF6 and IRAK1 and downstream target NF-κB after challenge with lipopolysaccharide (LPS) or wounding. Additionally, miR-146a overexpression suppressed the production of downstream inflammatory mediators including secreted cytokines IL-1α, IL-1β, IL-6 and IL-8, and chemokines CXCL1, CXCL2 and CXCL5. These cytokines and chemokines were upregulated in normal but not in diabetic LEC during wounding. Furthermore, we achieved normalized levels of altered secreted cytokines and chemokines in diabetic wounded LEC via specific inhibition of miR-146a. Our study documented significant impact of miR-146a on the expression of inflammatory mediators at the mRNA and protein levels during acute inflammatory responses and wound healing, providing insights into the regulatory role of miR-146a in corneal epithelial homeostasis in normal and diabetic conditions.
Identifiants
pubmed: 35690236
pii: S1542-0124(22)00046-5
doi: 10.1016/j.jtos.2022.06.001
pmc: PMC10200270
mid: NIHMS1900567
pii:
doi:
Substances chimiques
Cytokines
0
Inflammation Mediators
0
MIRN146 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
92-100Subventions
Organisme : NEI NIH HHS
ID : R01 EY013431
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY025377
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029829
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY031377
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
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