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.

DNA methylation is associated with expression level changes of galectin gene in mantle wound healing process of pearl oyster, Pinctada fucata

“…Galectins in oysters, such as Crassostrea virginica [9], Crassostrea gigas [10] and scallop Argopectens irradians [11], have been reported to play roles in immune response. Besides, galectins are implicated in epithelial cell adhesion and wound repair [6,12,13]. In the case of P. fucata, the cDNAs of a galectin with multiple carbohydrate-recognition domains, and a tandem-repeat galectin contained two tandem carbohydrate recognition domains have been cloned, and the mRNA expression levels were up-regulated after bacterial invasion [4,5].…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…There is controversy not only with respect to the presence of myofibroblasts in keloid tissues [2,4,8,44] but also over the conversion in vivo of dermal fibroblasts into myofibroblasts in wound healing induced by Gal-1 [24,26,45]. In fact, different studies in vivo have reported that myofibroblasts are the predominant cell type present in keloid tissues [4,44] while others report that they are absent [2,8] and that in animal models Gal-1 induces the conversion of dermal fibroblasts into myofibroblasts during wound healing [23,45].…”

“…There is controversy not only regarding the presence of myofibroblasts in keloid tissues [2,4,8,44] but also regarding the conversion of fibroblasts into myofibroblasts by Gal-1 [24,26,45]; therefore, we sought to determine by double-immunofluorescence staining whether α-SM actin, the most common marker for myofibroblasts identification [46], was present in the fibroblasts of keloid tissues examined. Immunolocalization demonstrated that α-SM actin was completely absent in the fibroblasts expressing Gal-1 as well as in those that did not it (Fig.…”

“…A protein that has been implicated in the wound healing process [23,24], conversion of fibroblasts into myofibroblasts [24][25][26] and production of ECM components [26], inflammation [27], and generation of galectin-glycan complexes [28][29][30], is galectin-1 (Gal-1). Gal-1 is a member of the galectin family that has high affinity for N-acetylLactosamine (LacNAc) disaccharides in both Nand O-glycans and is differentially expressed by various normal and pathological tissues [31].…”

Galectin-1 expression is associated with tumour immunity and prognosis in gingival squamous cell carcinoma

“…Several in vitro studies using human cancer cell lines8 12 14 24 or animal tissue25 revealed that Gal-1 promotes angiogenesis and lymphangiogenesis, and induces apoptosis of activated T cells 5 13. These studies demonstrated that inhibition of Gal-1 promotes immunosuppression and reduces tumour metastasis 25–27.…”