RT info:eu-repo/semantics/article
T1 Cutaneous Wound Healing in Diabetic Mice Is Improved by Topical Mineralocorticoid Receptor Blockade
A1 Nguyen, Van Tuan
A1 Farman, Nicolette
A1 Palacios-Ramirez, Roberto
A1 Sbeih, Maria
A1 Behar-Cohen, Francine
A1 Aractingi, Sélim
A1 Jaisser, Frederic
K1 mineralocorticoid receptor
K1 wound healing
K1 diabetes
AB 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.
PB ELSEVIER
SN 0022-202X
YR 2020
FD 2020
LK https://uvadoc.uva.es/handle/10324/66276
UL https://uvadoc.uva.es/handle/10324/66276
LA spa
NO J Invest Dermatol  . 2020 Jan;140(1):223-234.e7
NO Producción Científica
DS UVaDOC
RD 09-may-2024