Wound healing delay is among the deleterious effects of over-activation of the mineralocorticoid receptor (MR) induced by dermocorticoids treatment. The role of dermal inflammation and angiogenesis in the benefit of MR blockade is unclear. Herein, using the topical pretreatment mice with dermocorticoid clobetasol as model to study, we investigated the impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype after five days post-wounding. Our results showed that topically treatment with pharmacological inhibition of the MR (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 (M2) macrophages versus pro-inflammatory (M1) macrophages in wounds treated by canrenoate (pre-Clo + PBS: 0.47 vs pre-Clo + Canre: 0.8). Furthermore, MR blockade improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Indeed, the blood vessel density in wound beds of pre-Clo + PBS versus pre-Clo + Canre mice were 3.35% vs 6.2%, respectively. This improvement of dermal angiogenesis was associated with the increased number of endothelial cells and the upregulated expression of pro-angiogenic factors in dermal wounds. Moreover, similar experiments on murine genetic model of the MR deficiency in myeloid cells demonstrated that deletion of MR in myeloid cells reproduced the benefits of topical pharmacological MR blockade.

LB070 - Myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.