Cutaneous Wound Healing in Diabetic Mice Is Improved by Topical Mineralocorticoid Receptor Blockade.

Autor:	Nguyen VT; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France; Laboratory of progenitors and endothelial cells during and after pregnancy, INSERM UMR 938, Centre de Recherche St Antoine, Sorbonne Université, Paris, France; Department of Basic Science, Thai Nguyen University of Agriculture and Forestry, Thainguyen, Vietnam., Farman N; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France., Palacios-Ramirez R; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France., Sbeih M; Laboratory of progenitors and endothelial cells during and after pregnancy, INSERM UMR 938, Centre de Recherche St Antoine, Sorbonne Université, Paris, France., Behar-Cohen F; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France; Faculty of Medicine, Université Paris Descartes, Paris, France., Aractingi S; Laboratory of progenitors and endothelial cells during and after pregnancy, INSERM UMR 938, Centre de Recherche St Antoine, Sorbonne Université, Paris, France; Faculty of Medicine, Université Paris Descartes, Paris, France; Department of Dermatology, Hôpital Cochin-Tarnier, Paris, France., Jaisser F; INSERM, Centre de Recherche des Cordeliers, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France; INSERM, Clinical Investigation Centre 1433, Vandoeuvre-lès-Nancy, France. Electronic address: frederic.jaisser@inserm.fr.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2020 Jan; Vol. 140 (1), pp. 223-234.e7. Date of Electronic Publication: 2019 Jul 03.
DOI:	10.1016/j.jid.2019.04.030
Abstrakt:	Skin ulcers resulting from impaired wound healing are a serious complication of diabetes. Unresolved inflammation, associated with the dysregulation of both the phenotype and function of macrophages, is involved in the poor healing of diabetic wounds. Here, we report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR small interfering RNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected. The beneficial effect of canrenoate is associated with an increased ratio of anti-inflammatory M2 macrophages to proinflammatory M1 macrophages in diabetic wounds. Furthermore, we show that MR blockade leads to downregulation of the MR target, LCN2, which may facilitate macrophage polarization toward the M2 phenotype and improve impaired angiogenesis in diabetic wounds. Indeed, diabetic LCN2-deficient mice showed improved wound healing associated with macrophage M2 polarization and angiogenesis. In addition, recombinant LCN2 protein prevented IL-4-induced macrophage switch from M1 to M2 phenotype. In conclusion, topical MR blockade accelerates skin wound healing in diabetic mice via LCN2 reduction, M2 macrophage polarization, prevention of inflammation, and induction of angiogenesis. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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