Use of NGAL Inhibitors for treating chronic wound
Chronic wounds and in particular diabetic ulcers 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, the inventor report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR siRNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected. Furthermore, they show that MR blockade leads to downregulation of the MR target, lipocalin 2 (Lcn or NGAL), which may facilitate macrophage polarization towards 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 IL4-induced macrophages switch from M1 to M2 phenotype. In conclusion, inhibiting the activity or expression of NGAL would very suitable for the treatment of chronic wounds.
- J Invest Dermatol. 2020 Jan;140(1):223-234.e7. doi: 10.1016/j.jid.2019.04.030. Epub 2019 Jul 3.