title: Lumican binds ALK5 to promote epithelium wound healing.
abstract: 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.
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Vivien Jane
authors.initials: VJ
authors.lastname: Coulson-Thomas
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Tarsis Ferreira
authors.initials: TF
authors.lastname: Gesteira
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Mindy K
authors.initials: MK
authors.lastname: Call
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Wakayama Medical College, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.affiliation: Gavin Herbert Eye Institute, Ophthalmology, University of California Irvine, Irvine, California, United States of America.
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
authors.affiliation: Deparment of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism*; D000071234:Lumican; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C490948:KERA protein, human; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D007632:Keratan Sulfate; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse