PloS one, 2013-12, Vol.8 (12), p.e82730
2013
Details
- Autor(en) / Beteiligte
- Titel
- Lumican binds ALK5 to promote epithelium wound healing
- Ist Teil von
- PloS one, 2013-12, Vol.8 (12), p.e82730
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0082730Titel-ID: cdi_plos_journals_1469304723
- Format
- –
- Schlagworte
- Adult, Aged, Amino acids, Animals, Blotting, Western, Bone morphogenetic proteins, Care and treatment, Cell cycle, Cell growth, Cell Line, Cell proliferation, Cell surface, Cells, Cultured, Chondroitin Sulfate Proteoglycans - genetics, Chondroitin Sulfate Proteoglycans - metabolism, Collagen, E coli, Epithelium, Extracellular matrix, Female, Fluorescent Antibody Technique, Gene expression, Goods and services tax, Growth factors, Humans, Inflammation, Keratan Sulfate - genetics, Keratan Sulfate - metabolism, Leucine, Lumican, Male, Mice, Mice, Knockout, Middle Aged, Molecular docking, Molecular dynamics, Molecular Dynamics Simulation, Molecular weight, Physics, Post-translation, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - metabolism, Proteins, Proteoglycans - genetics, Proteoglycans - metabolism, Receptors, Transforming Growth Factor beta - genetics, Receptors, Transforming Growth Factor beta - metabolism, Transforming growth factor, Transforming growth factor-b, Wound care, Wound healing, Wound Healing - genetics, Wound Healing - physiology, Wounds and injuries