Song Xu, Chen Yaqin, Chen Xiangxiu, Zhao Xinghong, Zou Yuanfeng, Li Lixia, Zhou Xun, Li Mingyue, Zhang Dongmei, Ye Gang, Jia Renyong, Yin Zhongqiong
Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Int J Biol Macromol. 2023 Jul 31;244:125088. doi: 10.1016/j.ijbiomac.2023.125088. Epub 2023 Jun 2.
Tannic acid (TA) and its extraction were traditionally used for treatment of traumatic bleeding in China, and in the previous study we have demonstrated that TA could accelerate cutaneous wound healing in rats. We attempted to decipher the mechanism of TA in promoting wound healing. In this study, we found that TA could enhance the growth of macrophages and inhibit the release of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8 and IL-10) through inhibition of NF-κB/JNK pathway. TA activated Erk1/2 pathway, leading to increased expressions of growth factors, bFGF and HGF. Scratch study revealed that TA did not directly regulate the migration function of fibroblasts, but could indirectly enhance fibroblasts migration by the supernatant of TA-treated macrophages. Transwell study further proved that TA stimulates macrophages to secrete exosomes enriched in miR-221-3p by activating the p53 signaling pathway, and the exosomes entered into the fibroblast cytoplasm and bound to 3'UTR of target gene CDKN1b which induced decreased expression level of CDKN1b, leading to promoting fibroblast migration. This study provided new insights into how TA accelerates wound healing in the inflammatory and proliferative phases of wound healing.
在中国，鞣酸（TA）及其提取物传统上用于治疗外伤性出血，并且在先前的研究中我们已经证明TA可以加速大鼠皮肤伤口愈合。我们试图解读TA促进伤口愈合的机制。在本研究中，我们发现TA可通过抑制NF-κB/JNK通路来增强巨噬细胞的生长并抑制炎性细胞因子（IL-1β、IL-6、TNF-α、IL-8和IL-10）的释放。TA激活Erk1/2通路，导致生长因子bFGF和HGF的表达增加。划痕实验表明，TA不会直接调节成纤维细胞的迁移功能，但可通过TA处理的巨噬细胞的上清液间接增强成纤维细胞的迁移。Transwell实验进一步证明，TA通过激活p53信号通路刺激巨噬细胞分泌富含miR-221-3p的外泌体，这些外泌体进入成纤维细胞细胞质并与靶基因CDKN1b的3'UTR结合，导致CDKN1b表达水平降低，从而促进成纤维细胞迁移。本研究为TA如何在伤口愈合的炎症期和增殖期加速伤口愈合提供了新的见解。
