Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

Abstract

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV in the skin cells. Further studies showed that gremlin activated VEGFR2 downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative mutation largely inhibited gremlin-mediated skin cell protection against UV. At last, we show that gremlin dramatically inhibited UV-induced ROS production and DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant.

The effect of Cyanidin-3-o-glucoside on UVA-induced damage in human dermal fibroblasts

“…22 In particular, the cytotoxic activities of ROS lead to apoptosis. 23 In our experiments, the cell survival rate was decreased by UVA ( Figure 2B), and HDFs showed increased ROS levels ( Figure 3A,B,D) as well as increased apoptosis (Figure 3C,E) when exposed to 12 J/cm 2 of UVA.…”

K6PC-5 Activates SphK1-Nrf2 Signaling to Protect Neuronal Cells from Oxygen Glucose Deprivation/Re-Oxygenation

“…The mRNA primers for SphK1 were as described previously [25]. The mRNA primers for nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO1), NAD(P)H quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase catalytic subunit (GCLC), and GAPDH were also described [26,27].…”

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling

“…Our recent study demonstrated that gremlin activated Nrf2 and inhibited UV-induced ROS production and subsequent DNA single strand break (SSB) [7]. Since MHY1485 activated Nrf2 signaling, its potential anti-oxidant activity was analyzed next.…”

“…The ROS fluorescent intensity of treatment group was normalized to that of untreated control group [4, 7]. …”