Galectin-1 Accelerates Wound Healing by Regulating the Neuropilin-1/Smad3/NOX4 Pathway and ROS Production in Myofibroblasts

• Published in: Journal of investigative dermatology Vol. 135; no. 1; pp. 258 - 268
• Main Authors: Lin, Yueh-Te, Chen, Jhih-Sian, Wu, Ming-Heng, Hsieh, I-Shan, Liang, Chen-Hsien, Hsu, Cheng-Lung, Hong, Tse-Ming, Chen, Yuh-Ling
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2015; Elsevier Limited
• Subjects: Animals; Cell Movement - physiology; Cell Proliferation; Cells, Cultured; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Disease Models, Animal; Fibroblasts - cytology; Fibroblasts - metabolism; Galectin 1 - genetics; Galectin 1 - metabolism; Galectin 1 - pharmacology; Gingiva - cytology; HEK293 Cells; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidase 4; NADPH Oxidases - metabolism; Neuropilin-1 - metabolism; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Skin - injuries; Skin - metabolism; Smad3 Protein - metabolism; Wound Healing - drug effects; Wound Healing - physiology
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1038/jid.2014.288

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.