title: Proteoglycan from salmon nasal cartridge [corrected] promotes in vitro wound healing of fibroblast monolayers via the CD44 receptor.
abstract: Proteoglycans (PGs) are involved in various cellular functions including cell growth, adhesion, and differentiation; however, their physiological roles are not fully understood. In this study, we examined the effect of PG purified from salmon nasal cartilage (SNC-PG) on wound closure using tissue-cultured cell monolayers, an in vitro wound-healing assay. The results indicated that SNC-PG significantly promoted wound closure in NIH/3T3 cell monolayers by stimulating both cell proliferation and cell migration. SNC-PG was effective in concentrations from 0.1 to 10μg/ml, but showed much less effect at higher concentrations (100-1000μg/ml). The effect of SNC-PG was abolished by chondroitinase ABC, indicating that chondroitin sulfates (CSs), a major component of glycosaminoglycans (GAGs) in SNC-PG, are crucial for the SNC-PG effect. Furthermore, chondroitin 6-sulfate (C-6-S), a major CS of SNC-PG GAGs, could partially reproduce the SNC-PG effect and partially inhibit the binding of SNC-PG to cells, suggesting that SNC-PG exerts its effect through an interaction between the GAGs in SNC-PG and the cell surface. Neutralization by anti-CD44 antibodies or CD44 knockdown abolished SNC-PG binding to the cells and the SNC-PG effect on wound closure. These results suggest that interactions between CS-rich GAG-chains of SNC-PG and CD44 on the cell surface are responsible for the SNC-PG effect on wound closure.
authors.affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Ito
authors.affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Mechanobiology Institute Singapore, National University of Singapore, Singapore 117411, Singapore. Electronic address: msokabe@med.nagoya-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D053674:Aggrecans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D002809:Chondroitin Sulfates / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D055171:Nasal Cartilages / Q000737:chemistry*; D012474:Salmon; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D053674:Aggrecans; D018960:Hyaluronan Receptors; D002809:Chondroitin Sulfates
keywords: CD44; Chondroitin sulfate; Proteoglycan; Salmon nasal cartilage; Wound healing