A Frog Skin‐Derived Peptide Targeting SCD1 Exerts Radioprotective Effects Against Skin Injury by Inhibiting STING‐Mediated Inflammation

Abstract

The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation‐induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation‐induced frog skin peptide‐2 (RIFSP‐2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl‐CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP‐2 based on streptavidin‐biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP‐2 following radiation. Moreover, the decreased MUFA limited radiation‐induced and STING‐mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP‐2 and retarded tissue repair process. Altogether, RIFSP‐2 restrains radiation‐induced activation of SCD1‐MUFA‐STING axis. Thus, the stress‐induced amphibian peptides can be a bountiful source of novel radiation mitigators.

UV radiation‐induced peptides in frog skin confer protection against cutaneous photodamage through suppressing MAPK signaling

“…And the UV-VIS and multi-omics in our recent research, has uncovered significant alterations in the activity of peptidases or endopeptidases within irradiated skin tissues. 17 In the current study, we examined the peptide profile after UVB radiation, in which skin tissues were grinded for sonication and the supernatants were applied to 10 kDa MWCO filters. The results showed an increased expression of small molecule gene-coding peptides (named UIFSPs) after intermittent UVB exposure, and peptide annotation revealed that UVB may act on structural proteins and induce UIFSPs production.…”

“…WS1 and HaCaT cells were seeded in a 96‐well plate at a density of 1 × 10 4 cells per well. 17 Then, cell viability was measured using the CCK‐8 according to the manufacturer's protocol, with a BioTek reader (Synergy HTX).…”

“…In our previous work, we found that 30 Gy electron beams altered the endogenous substances in frog skin tissues and induced RIFSP‐2 expression in which RIFSP‐2 serves as a promising radiation mitigator. 17 Herein, we established an inducibility model of P. nigromaculatus by repetitive UVB exposure and observed the physiological adaptations in frogs in response to UVB. By virtue of the peptidomic analysis, we analyzed the molecular basis of UV adaptation and identified the promising pharmacological peptides, which are named as UV‐induced frog skin peptides (UIFSPs).…”