Amphibian-derived peptide homodimer promotes regeneration of skin wounds.

Abstract

Despite the increasing treatments in skin wound repair, existing therapeutic drugs cannot meet current needs. As such, skin wound repair remains a considerable clinical challenge, and thus the discovery of new pro-healing agents is crucial. Here, we identified the first naturally occurring peptide homodimer named as OA-GP11 dimer (OA-GP11d) from Odorrana andersonii (odorous frog) through the combinational methods of peptidomics and genomics. OA-GP11d was linked by the intramolecular disulfide formed by the 10th cysteine residues from the monomer of peptide with sequence of GPLSGINAECM, which effectively promoted the repair of full-thickness and burn wounds in mice. The underlying molecular mechanisms revealed that OA-GP11d not only accelerated the migration and cell-scratch healing of mouse keratinocytes, but also activated the mitogen-activated protein kinases (MAPKs) signaling pathway (phosphorylation of p38 and ERK subgroups) in immortalized human keratinocytes (HaCaT). Besides, OA-GP11d reduced the phosphorylation of nuclear factor-κB (NF-κB) and inhibitor of NF-κB (I-κB) induced by lipopolysaccharide stimulation in mouse macrophages, and inhibited the release of associated inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6. OA-GP11d is the first identified naturally occurring peptide dimer with significant pro-healing potency. Our results highlight the importance of amphibians as a source of novel pro-healing agents and suggest OA-GP11d as a potential new pro-regenerative drug candidate.

• Authors: Yang Fu, Chao Li, Xiaojie Li, Lin Zeng, Yinglei Wang, Zhe Fu, Longjun Shu, Yixiang Liu, Naixin Liu, Ying Yang, Jing Tang, Ying Wang, Xinwang Yang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 146 Pg. 112539 (Feb 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 34923337 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Amphibian Proteins
• NF-kappa B
• Oligopeptides
• Tumor Necrosis Factor-alpha

Topics

• Amino Acid Sequence
• Amphibian Proteins (chemistry, pharmacology)
• Animals
• Keratinocytes (drug effects)
• Mice
• NF-kappa B (metabolism)
• Oligopeptides (chemistry, pharmacology)
• Ranidae
• Tumor Necrosis Factor-alpha (metabolism)
• Wound Healing (drug effects)