Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of small molecular peptides (SMPs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of SMPs, the effect of SMPs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that SMPs consisted of polypeptides with a molecular weight of 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that SMPs possess a procoagulant effect, but no antibacterial activity. Results of in vivo experiments indicated that SMPs inhibit inflammatory response by secretion of anti-inflammatory factor IL-10 during the inflammatory phase; during the proliferative phase, SMPs promote the proliferation of fibroblasts and keratinocytes. The secretion of transforming growth factor-β1 and cyclin D1 accelerates the epithelialization and contraction of wounds. In the proliferative phase, SMPs effectively promote collagen deposition and partially inhibit superficial scar hyperplasia. These results show that SMPs promotes dermal wound healing in mice and have a tremendous potential for development and utilization in skin wound healing.

Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of APs, the effect of APs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that APs consisted of polypeptides with molecular weights in the range 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that mice in APs-L group which were fed a low dose of APs (0.5 g/kg bw) had a shortened epithelialization time due to a shortening inflammatory period (p < 0.05). Mechanistically, this relied on its specific ability to promote the proliferation of CD31, FGF and EGF which accelerated the percentage of wound closure. Moreover, the APs-L group mice had enhanced collagen synthesis and increased type III collagen content in their wounds through a TGF-β/Smad signaling pathway (p > 0.05). Consequently, scar formation was inhibited and wound healing efficiency was significantly improved. These results show that the APs of Pinctada martensii promote dermal wound healing in mice and have tremendous potential for development and utilization in skin wound healing.

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Previous studies found that both oral and topical administration of enzymatic digestion products < 3 K Da ultrafiltration fractions of Pinctada martensii mantle (PMPs) had pro-healing effects. Thus, we further purified them by Sephadex-G25 and screened them by cellular assays to obtain Pinctada martensii purified peptides (PMPPs). In this study, we explored the mechanism of PMPPs on wound healing by in vivo, in vitro, and in silico experiments. LC-MS/MS results showed that PMPPs consisted of 33 peptides with molecular weights ranging from 758.43 to 2014.04 Da, and the characteristic peptide was Leu-Asp. The results of cellular assays showed that PMPPs promoted the proliferation of human skin fibroblasts (HSF) (135%) and human immortalized keratinocyte (HaCaT) cells (125%) very significantly at 12.5 μg/mL. The in vivo results showed that PMPPs could achieve scarless healing by inhibiting the inflammatory response, accelerating the epithelialization process, and regulating collagen I/III ratio. The optimal peptide sequence FAFQAEIAQLMS of PMPPs was screened for key protein receptors in wound healing (EGFR1, FGFR1, and MMP-1) with the help of molecular docking technique, which also showed to be the key pro-healing active peptide sequence. Therefore, it may provide a therapeutic strategy with great potential for wound healing.