The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway.
The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway.
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DOI：
10.3389/fimmu.2021.712781
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发表时间：
2021
影响因子：
7.3
通讯作者：
Niyonsaba F
中科院分区：
文献类型：
--
作者：
Takahashi M;Umehara Y;Yue H;Trujillo-Paez JV;Peng G;Nguyen HLT;Ikutama R;Okumura K;Ogawa H;Ikeda S;Niyonsaba F
除了抗菌活性外，皮肤源性抗菌肽人 β-防御素-3 (hBD-3) 还可促进角质形成细胞增殖和迁移，从而启动伤口愈合过程；然而，它对成纤维细胞（负责伤口愈合的主要细胞类型）的影响仍不清楚。我们研究了 hBD-3 在人成纤维细胞的细胞迁移、增殖和血管生成生长因子产生中的作用，并评估了 hBD-3 在促进伤口愈合和血管生成方面的体内作用。 hBD-3治疗后，小鼠伤口愈合更快，在伤口愈合早期出现中性粒细胞和巨噬细胞聚集，4天后这些吞噬细胞减少。与对照小鼠相比，hBD-3 处理的伤口还显示出成纤维细胞和新形成血管数量的增加。此外，hBD-3处理的伤口中各种血管生成生长因子的表达增加。此外，体外研究表明，hBD-3可增强成纤维细胞生长因子、血小板源性生长因子和血管内皮生长因子等血管生成生长因子的分泌，并诱导人成纤维细胞的迁移和增殖。 hBD-3 介导的成纤维细胞激活涉及成纤维细胞生长因子受体 1 (FGFR1)/Janus 激酶 2 (JAK2)/信号转导器和转录激活剂 3 (STAT3) 通路，通路特异性抑制剂的抑制作用证明了这一点。我们确实证实 hBD-3 增强了 FGFR1、JAK2 和 STAT3 的磷酸化。总的来说，当前的研究提供了新的证据，表明 hBD-3 可能通过其促进伤口愈合、血管生成和成纤维细胞活化的能力而成为治疗伤口的潜在候选者。
In addition to its antimicrobial activity, the skin-derived antimicrobial peptide human β-defensin-3 (hBD-3) promotes keratinocyte proliferation and migration to initiate the wound healing process; however, its effects on fibroblasts, which are the major cell type responsible for wound healing, remain unclear. We investigated the role of hBD-3 in cell migration, proliferation and production of angiogenic growth factors in human fibroblasts and evaluated the in vivo effect of hBD-3 on promoting wound healing and angiogenesis. Following hBD-3 treatment, the mouse wounds healed faster and showed accumulation of neutrophils and macrophages in the early phase of wound healing and reduction of these phagocytes 4 days later. hBD-3-treated wounds also displayed an increased number of fibroblasts and newly formed vessels compared to those of the control mice. Furthermore, the expression of various angiogenic growth factors was increased in the hBD-3-treated wounds. Additionally, in vitro studies demonstrated that hBD-3 enhanced the secretion of angiogenic growth factors such as fibroblast growth factor, platelet-derived growth factor and vascular endothelial growth factor and induced the migration and proliferation of human fibroblasts. The hBD-3-mediated activation of fibroblasts involves the fibroblast growth factor receptor 1 (FGFR1)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways, as evidenced by the inhibitory effects of pathway-specific inhibitors. We indeed confirmed that hBD-3 enhanced the phosphorylation of FGFR1, JAK2 and STAT3. Collectively, the current study provides novel evidence that hBD-3 might be a potential candidate for the treatment of wounds through its ability to promote wound healing, angiogenesis and fibroblast activation.
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