The myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing.
healing
macrophages
mineralocorticoid
skin
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
31
05
2022
received:
09
10
2021
accepted:
05
07
2022
pubmed:
22
7
2022
medline:
5
11
2022
entrez:
21
7
2022
Statut:
ppublish
Résumé
Delayed wound healing is among the deleterious consequences of over-activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown. Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post-wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells. Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid-pretreated mouse skin. This effect was associated with a higher ratio of anti-inflammatory macrophages versus pro-inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro-angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade. Topical MR antagonism facilitates the switching of macrophages towards an anti-inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.
Sections du résumé
BACKGROUND AND PURPOSE
Delayed wound healing is among the deleterious consequences of over-activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown.
EXPERIMENTAL APPROACH
Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post-wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells.
KEY RESULTS
Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid-pretreated mouse skin. This effect was associated with a higher ratio of anti-inflammatory macrophages versus pro-inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro-angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade.
CONCLUSION AND IMPLICATIONS
Topical MR antagonism facilitates the switching of macrophages towards an anti-inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.
Identifiants
pubmed: 35861949
doi: 10.1111/bph.15932
pmc: PMC9826027
doi:
Substances chimiques
Receptors, Mineralocorticoid
0
Glucocorticoids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5222-5232Informations de copyright
© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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