Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response.

Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response. Biochem Pharmacol. 2020 Feb 04;:113846 Authors: Wu R, Zhang H, Zhao M, Li J, Hu Y, Fu J, Pi J, Wang H, Xu Y Abstract Nuclear factor-E2-related factor 2 (Nrf2) is a master transcription factor in antioxidant response, protecting against oxidative damage and various diseases. Previous studies suggest that Nrf2 is suppressed in fibrotic skin and Nrf2 agonists represent a therapeutic strategy, which is mainly attributed to Nrf2 function in fibroblasts. However, constitutive activation of Nrf2 may endow cells with proliferation and survival advantage, facilitating skin tumorigenesis. Non-invasive and mild modulation of Nrf2 via topical application may be helpful. Keratinocytes, which are essential for epidermal formation and function maintenance, have been shown to modulate differentiation of fibroblasts in different stages of fibrosis. In this respect, the role of Nrf2 in keratinocytes in skin fibrosis remains elusive. In the present study, bleomycin (BLM)-induced skin fibrosis model was applied to keratinocyte-specific Nrf2 knockout (Nrf2(K)-KO) mice generated with Keratin 14-Cre/loxp system. BLM treatment significantly suppressed Nrf2 expression in the epidermis. Nrf2 deficiency in keratinocytes exacerbated BLM-induced skin fibrosis according to dermal thickness, and immunostaining of collagen and α-SMA. One-dose BLM treatme...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research