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Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain
Author(s) -
Zhu Qi,
Mangukiya Hitesh Bhagavanbhai,
Mashausi Dhahiri Saidi,
Guo Hao,
Negi Hema,
Merugu Siva Bharath,
Wu Zhenghua,
Li Dawei
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14155
Subject(s) - wound healing , extracellular matrix , cell migration , epidermis (zoology) , microbiology and biotechnology , zebrafish , angiogenesis , regeneration (biology) , cell adhesion , focal adhesion , chemistry , biology , cell , anatomy , cancer research , immunology , signal transduction , biochemistry , gene
Anterior gradient 2 ( AGR 2), a member of protein disulfide isomerase ( PDI ) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR 2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR 2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR 2 in mammalian wound healing remains unknown. This study aimed to investigate AGR 2 expression and its function during skin wound healing and the possible application of external AGR 2 in cutaneous wound to accelerate the healing process. Our results showed that AGR 2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR 2 significantly accelerated wound‐healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR 2 also promoted the migration of Kera. and Fibro. in vitro in a dose‐dependent manner. The adhesion domain of AGR 2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR 2 gradient. These results indicate that recombinant AGR 2 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.