title: Galectin-1 accelerates wound healing by regulating the neuropilin-1/Smad3/NOX4 pathway and ROS production in myofibroblasts.
abstract: Myofibroblasts have a key role in wound healing by secreting growth factors and chemoattractants to create new substrates and proteins in the extracellular matrix. We have found that galectin-1, a β-galactose-binding lectin involved in many physiological functions, induces myofibroblast activation; however, the mechanism remains unclear. Here, we reveal that galectin-1-null (Lgals1(-/-)) mice exhibited a delayed cutaneous wound healing response. Galectin-1 induced myofibroblast activation, migration, and proliferation by triggering intracellular reactive oxygen species (ROS) production. A ROS-producing protein, NADPH oxidase 4 (NOX4), was upregulated by galectin-1 through the neuropilin-1/Smad3 signaling pathway in myofibroblasts. Subcutaneous injection of galectin-1 into wound areas accelerated the healing of general and pathological (streptozotocin-induced diabetes mellitus) wounds and decreased the mortality of diabetic mice with skin wounds. These findings indicate that galectin-1 is a key regulator of wound repair that has therapeutic potential for pathological or imperfect wound healing.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yueh-Te
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jhih-Sian
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Institute for Translational Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Heng
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Shan
authors.initials: IS
authors.lastname: Hsieh
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: tmhong@mail.ncku.edu.tw.
authors.forename: Tse-Ming
authors.initials: TM
authors.lastname: Hong
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: yuhling@mail.ncku.edu.tw.
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D039942:Neuropilin-1 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000293:injuries / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D037483:Galectin 1; C445499:LGALS1 protein, human; D017382:Reactive Oxygen Species; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D039942:Neuropilin-1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human