The myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing.

Autor: Nguyen VT; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.; Department of Basic Science, Thai Nguyen University of Agriculture and Forestry, Thainguyen, Vietnam., Ngo QT; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.; Laboratory of Cutaneous Biology, INSERM U1016, Cochin Institute, Université Paris Cité, Paris, France., Ramirez RP; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France., Nakamura T; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France., Farman N; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France., Aractingi S; Laboratory of Cutaneous Biology, INSERM U1016, Cochin Institute, Université Paris Cité, Paris, France.; Department of Dermatology, Cochin Hospital, Paris, France., Jaisser F; INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2022 Dec; Vol. 179 (23), pp. 5222-5232. Date of Electronic Publication: 2022 Sep 02.
DOI: 10.1111/bph.15932
Abstrakt: 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.
(© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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