Lumican Binds ALK5 to Promote Epithelium Wound Healing

作者：Yamanaka Osamu; Yuan Yong; Coulson Thomas Vivien Jane; Gesteira Tarsis Ferreira; Call Mindy K; Zhang Yujin; Zhang Jianhua; Chang Shao Hsuan; Xie Changchun; Liu Chia Yang; Saika Shizuya; Jester James V; Kao Winston W Y^*

来源：PLos One, 2013, 8(12): e82730.

DOI：10.1371/journal.pone.0082730

Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-beta receptor 1 (ALK5) was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC(13) peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo.

• 出版日期2013-12-18