Search

Overexposure to ultraviolet light (UV) has become a major dermatological problem since the intensity of ultraviolet radiation is increasing. As an adaption to outside environments, amphibians gained an excellent peptide‐based defense system in their naked skin from secular evolution. Here, we first determined the adaptation and resistance of the dark‐spotted frogs (Pelophylax nigromaculatus) to constant ultraviolet B (UVB) exposure. Subsequently, peptidomics of frog skin identified a series of novel peptides in response to UVB. These UV‐induced frog skin peptides (UIFSPs) conferred significant protection against UVB‐induced death and senescence in skin cells. Moreover, the protective effects of UIFSPs were boosted by coupling with the transcription trans‐activating (TAT) protein transduction domain. In vivo, TAT‐conjugated UIFSPs mitigated skin photodamage and accelerated wound healing. Transcriptomic profiling revealed that multiple pathways were modulated by TAT‐conjugated UIFSPs, including small GTPase/Ras signaling and MAPK signaling. Importantly, pharmacological activation of MAPK kinases counteracted UIFSP‐induced decrease in cell death after UVB exposure. Taken together, our findings provide evidence for the potential preventive and therapeutic significance of UIFSPs in UV‐induced skin damage by antagonizing MAPK signaling pathways. In addition, these results suggest a practicable alternative in which potential therapeutic agents can be mined from organisms with a fascinating ability to adapt. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Radiogenic skin injury (RSI) is a common complication during cancer radiotherapy or accidental exposure to radiation. The aim of this study is to investigate the metabolism of bile acids (BAs) and their derivatives during RSI. Rat skin tissues were irradiated by an X-ray linear accelerator. The quantification of BAs and their derivatives were performed by liquid chromatography–mass spectrometry (LC–MS)-based quantitative analysis. Key enzymes in BA biosynthesis were analyzed from single-cell RNA sequencing (scRNA-Seq) data of RSI in the human patient and animal models. The in vivo radioprotective effect of deoxycholic acid (DCA) was detected in irradiated SD rats. Twelve BA metabolites showed significant differences during the progression of RSI. Among them, the levels of cholic acid (CA), DCA, muricholic acid (MCA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycohyodeoxycholic acid (GHCA), 12-ketolithocholic acid (12-ketoLCA) and ursodeoxycholic acid (UDCA) were significantly elevated in irradiated skin, whereas lithocholic acid (LCA), tauro-β-muricholic acid (Tβ-MCA) and taurocholic acid (TCA) were significantly decreased. Additionally, the results of scRNA-Seq indicated that genes involved in 7a-hydroxylation process, the first step in BA synthesis, showed pronounced alterations in skin fibroblasts or keratinocytes. The alternative pathway of BA synthesis is more actively altered than the classical pathway after ionizing radiation. In the model of rat radiogenic skin damage, DCA promoted wound healing and attenuated epidermal hyperplasia. Ionizing radiation modulates the metabolism of BAs. DCA is a prospective therapeutic agent for the treatment of RSI. [ABSTRACT FROM AUTHOR]