TY - JOUR
T1 - Lumican binds ALK5 to promote epithelium wound healing
AU - Yamanaka, Osamu
AU - Yuan, Yong
AU - Coulson-Thomas, Vivien Jane
AU - Gesteira, Tarsis Ferreira
AU - Call, Mindy K.
AU - Zhang, Yujin
AU - Zhang, Jianhua
AU - Chang, Shao Hsuan
AU - Xie, Changchun
AU - Liu, Chia Yang
AU - Saika, Shizuya
AU - Jester, James V.
AU - Kao, Winston W.Y.
PY - 2013/12/18
Y1 - 2013/12/18
N2 - 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-β 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 LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo.
AB - 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-β 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 LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo.
UR - https://www.scopus.com/pages/publications/84893194712
U2 - 10.1371/journal.pone.0082730
DO - 10.1371/journal.pone.0082730
M3 - 文章
C2 - 24367547
AN - SCOPUS:84893194712
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e82730
ER -