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Pharmacol Res ; 163: 105296, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220421

RESUMO

Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence 'QNSYADLWCQFHYMC') from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-ß1 and TGF-ß3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis, and oral ulcers. Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.


Assuntos
Úlceras Orais/tratamento farmacológico , Peptídeos/uso terapêutico , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Fibrose , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peptídeos/farmacologia , Células RAW 264.7 , Ranidae , Pele/lesões , Pele/metabolismo , Pele/patologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta3/metabolismo
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