Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain
Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain
复制标题
在皮肤伤口中诱导前梯度 2，并通过其粘附域促进伤口愈合
DOI：
10.1111/febs.14155
复制
发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Dawei Li
中科院分区：
文献类型：
--
作者：
Qi Zhu;Hitesh Bhagavanbhai Mangukiya;Dhahiri Saidi Mashausi;Hao Guo;Hema Negi;Siva Bharath Merugu;Zhenghua Wu;Dawei Li
前梯度2 （AGR2）是蛋白二硫异构酶（PDI）家族的一员，位于细胞质中并分泌到细胞外基质中。AGR2的同源物与蝾螈的肢体再生和斑马鱼的伤口愈合有关。在哺乳动物中，AGR2影响肿瘤形成过程中的多种细胞信号通路，以及与新组织形成（如血管生成）相关的正常细胞功能。然而，AGR2在哺乳动物伤口愈合中的功能尚不清楚。本研究旨在探讨皮肤创面愈合过程中AGR2的表达及其功能，以及外源性AGR2在皮肤创面加速愈合过程中的应用前景。我们的研究结果表明，在皮肤切除后的迁移表皮舌和增生性表皮中诱导了AGR2的表达。局部应用重组AGR2可通过增加角化细胞（Kera.）的迁移和伤口附近成纤维细胞（Fibro.）的募集，显著加速伤口愈合过程。外部AGR2也促进了Kera的迁移。和纤维。在体外以剂量依赖的方式。在迁移的Fibro中，AGR2的粘附结构域是形成局灶粘附所必需的。，导致沿AGR2梯度的定向偏移。这些结果表明重组AGR2通过调控Kera促进皮肤创面愈合。和纤维。迁移，从而证明其潜在的效用，作为一种替代策略的治疗加速愈合急性或慢性皮肤伤口。
Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound‐healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose‐dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds.
登录
查看更多内容
较高脊椎动物中的分泌因子AG1缺少调节Danio Rerio的鳍的再生。
影响因子：
4.6
作者：
Ivanova AS;Shandarin IN;Ermakova GV;Minin AA;Tereshina MB;Zaraisky AG
通讯作者：
Zaraisky AG
影响因子：
56.9
作者：
MUSTOE, TA;PIERCE, GF;DEUEL, TF
通讯作者：
DEUEL, TF
影响因子：
11.2
作者：
Wang, Zheng;Hao, Ying;Lowe, Anson W.
通讯作者：
Lowe, Anson W.
影响因子：
--
作者：
Annalisa Pirrone;B. Hager;P. Fleckman
通讯作者：
Annalisa Pirrone;B. Hager;P. Fleckman
影响因子：
6.5
作者：
Mazzalupo, S;Wawersik, MJ;Coulombe, PA
通讯作者：
Coulombe, PA