Zong Junwei, Jiang Jun, Shi Peng, Liu Jing, Wang Weili, Li Bin, Zhao Tianda, Pan Taowen, Zhang Zhen, Bi Liyan, Diao Yunpeng, Wang Shouyu
Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Institute (College) of Integrative Medicine, Dalian Medical University Dalian 116011, China.
College of Pharmacy, Dalian Medical University Dalian 116044, China.
Am J Transl Res. 2020 Feb 15;12(2):478-492. eCollection 2020.
Fatty acids (FAs) are potential therapeutic agents for cutaneous wound healing; however, the mechanisms underlying this effect have not been clearly defined. In this study, we extracted and characterized FAs from dried larvae and investigated the molecular basis by which FAs promote cutaneous wound healing. We first confirmed that FA sodium salts (FASSs) stimulated proliferation, migration, and tube formation of cultured (HUVECs) in a dose-dependent manner. We then showed that FASSs promoted endothelial-to-mesenchymal transition (EndMT), which plays an important role in stabilizing the neovasculature during angiogenesis. Mechanistically, FASSs up-regulated the expression of angiogenesis-related growth factors, platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA), and activated angiogenesis-related signaling pathways, AKT, ERK, and TGF-β/Smad3. In a rat acute cutaneous-wound model, FAs promoted wound healing. Following treatment, we further found that expression of anti-apoptosis-related factors (c-Myc and Bcl-2) was up-regulated and expression of apoptosis-related factors (p53 and Bad) was down-regulated. Our findings suggest that FAs can promote cutaneous wound healing by inducing angiogenesis, partly by activating AKT, ERK, and TGF-β/Smad3 signaling.
脂肪酸（FAs）是用于皮肤伤口愈合的潜在治疗剂；然而，这种作用的潜在机制尚未明确界定。在本研究中，我们从干燥的幼虫中提取并表征了脂肪酸，并研究了脂肪酸促进皮肤伤口愈合的分子基础。我们首先证实脂肪酸钠盐（FASSs）以剂量依赖性方式刺激培养的人脐静脉内皮细胞（HUVECs）的增殖、迁移和管形成。然后我们表明FASSs促进内皮-间充质转化（EndMT），这在血管生成过程中稳定新血管形成中起重要作用。从机制上讲，FASSs上调血管生成相关生长因子、血小板衍生生长因子（PDGF）、转化生长因子-β1（TGF-β1）和血管内皮生长因子A（VEGFA）的表达，并激活血管生成相关信号通路AKT、ERK和TGF-β/Smad3。在大鼠急性皮肤伤口模型中，脂肪酸促进伤口愈合。治疗后，我们进一步发现抗凋亡相关因子（c-Myc和Bcl-2）的表达上调，凋亡相关因子（p53和Bad）的表达下调。我们的研究结果表明，脂肪酸可通过诱导血管生成促进皮肤伤口愈合，部分是通过激活AKT、ERK和TGF-β/Smad3信号传导。
