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Pharmacol Res ; 163: 105296, 2021 01.
Article in English | MEDLINE | ID: mdl-33220421

ABSTRACT

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.


Subject(s)
Oral Ulcer/drug therapy , Peptides/therapeutic use , Skin/drug effects , Wound Healing/drug effects , Animals , Fibrosis , Male , Mice , Mitogen-Activated Protein Kinases/metabolism , Peptides/pharmacology , RAW 264.7 Cells , Ranidae , Skin/injuries , Skin/metabolism , Skin/pathology , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta3/metabolism
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