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福瓜乳胶原胱氨酸蛋白酶 Drupin 加速小鼠切口愈合。

Drupin, a cysteine protease from Ficus drupacea latex accelerates excision wound healing in mice.

机构信息

Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, Karnataka, India.

Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru, Karnataka, India.

出版信息

Int J Biol Macromol. 2020 Dec 15;165(Pt A):691-700. doi: 10.1016/j.ijbiomac.2020.09.215. Epub 2020 Sep 30.

DOI:10.1016/j.ijbiomac.2020.09.215
PMID:33010277
Abstract

Wound healing is a tightly regulated physiological process that restores tissue integrity after injury. Plant latex proteases (PLPs) are considered an integral part in herbal wound care as it interferes at different phases of the wound healing process. Although many studies have reported the involvement of PLPs in healing process, an in-depth investigation is required to understand the molecular mechanism. Hence, the effect of PLPs with fibrinolytic activity on wound healing was investigated systematically using mouse excision wound model. Among 29 latices from Ficus genus tested, Ficus drupacea exhibited potent fibrinolytic activity. Cysteine protease responsible for fibrinolysis was purified from the F. drupacea latex named it as drupin, tested for its wound healing efficacy. The accelerated wound healing was mediated by downregulation of matrix metalloprotease (MMP)-9 without altering MMP-8 expression. Besides, drupin enhanced the rate of collagen synthesis at the wound site by increasing arginase 1 activity. And also, drupin increased the expression of arginase 1 in macrophages and involved in cell proliferation, and migration via MAP kinase and PI3K/Akt pathways. Overall, the present study highlights the interference of drupin in wound healing by increased arginase 1 activity and collagen synthesis, and cell proliferation and migration.

摘要

创伤愈合是一个受严格调控的生理过程,可在受伤后恢复组织完整性。植物乳胶蛋白酶(PLPs)被认为是草药创伤护理的一个组成部分,因为它在创伤愈合过程的不同阶段发挥作用。尽管许多研究报告了 PLPs 参与愈合过程,但需要深入研究以了解其分子机制。因此,本研究使用小鼠切除伤口模型系统地研究了具有纤维蛋白溶解活性的 PLPs 对伤口愈合的影响。在测试的 29 种榕属乳胶中,榕属显示出很强的纤维蛋白溶解活性。从榕属乳胶中分离出负责纤维蛋白溶解的半胱氨酸蛋白酶,并将其命名为 drupin,测试其对伤口愈合的功效。通过下调基质金属蛋白酶(MMP)-9 而不改变 MMP-8 的表达来介导加速的伤口愈合。此外,drupin 通过增加精氨酸酶 1 的活性来增加伤口部位的胶原蛋白合成率。并且,drupin 通过 MAP 激酶和 PI3K/Akt 途径增加巨噬细胞中精氨酸酶 1 的表达,并参与细胞增殖和迁移。总之,本研究强调了 drupin 通过增加精氨酸酶 1 活性和胶原蛋白合成以及细胞增殖和迁移来干扰伤口愈合。

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