Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 02 2023
28 02 2023
Historique:
received:
11
12
2021
accepted:
13
02
2023
entrez:
28
2
2023
pubmed:
1
3
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.
Identifiants
pubmed: 36854749
doi: 10.1038/s41467-023-36665-z
pii: 10.1038/s41467-023-36665-z
pmc: PMC9975176
doi:
Substances chimiques
Antagomirs
0
Oligonucleotides
0
MIRN200 microRNA, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1129Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK076566
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114718
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128845
Pays : United States
Organisme : NIDDK NIH HHS
ID : R61 DK131909
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS042617
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS085272
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108014
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM077185
Pays : United States
Informations de copyright
© 2023. The Author(s).
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