Galectin 1 in dermatology: current knowledge and perspectives

Abstract

Gal 1, the first identified and best-studied prototypical member of the galectin family, is encoded in humans by the LGALS1 gene, which is located on chromosome 22 (q12) (10). It is a noncovalent homodimeric protein with a 14 kDa monomer that contains one CRD and preferentially recognizes galactose-β1-4-N-acetyl-glucosamine sequences on N-or O-linked glycans (11). AbstractGalectins are a family of soluble proteins that are widely distributed in nature and bind to a variety of glycoproteins and glycolipids bearing β-galactoside residues. They are involved in highly important processes at the molecular and cellular level in human cutaneous and extracutaneous tissues, and they exert biological effects of paramount importance through their interaction with cytoplasmic and nuclear proteins and the components of the cell surface and extracellular matrix. Galectin 1 (Gal 1), the first galectin isolated, is a noncovalent homodimeric protein with a 14 kDa monomer that contains one carbohydrate-recognition domain (CRD) and preferentially recognizes galactose-β1-4-N-acetyl-glucosamine sequences on N-or O-linked glycans. Gal 1 occurs intracellularly, extracellularly, and on the cell surface. In the last few years Gal 1 has emerged as a multifaceted protein that exerts a wide spectrum of regulatory effects in diverse normal and abnormal tissues and conditions, indicating a tremendous therapeutic potential. This review summarizes current knowledge on the expression of Gal 1 in normal and diseased human skin, its implications in the pathogenesis, diagnosis, and prognosis of cutaneous disorders, and the novel approach to the treatment of these disorders offered by the use of Gal 1 or its inhibitors/antagonists.

In contrast to melanocytes, keratinocytes of normal human adult interfollicular epidermis do not express galectin-1

“…The results of recent studies have shown that Gal 1 is overexpressed in melanomas (particularly in aggressive ones), and that this galectin is also involved in the mechanisms underlying the escape of melanoma cells from immune surveillance, metastatic progression, and the protection of melanomas from the cytotoxic effects of chemotherapy and radiotherapy (13,(16)(17)(18). These findings, together with the immunosuppressive, proangiogenic, and tumorigenic potential of Gal 1, support the hypothesis that this galectin may serve as a promising molecular target for the development of new Gal 1 inhibitors that could be used either alone or in combination with chemotherapy and radiotherapy in the fight against melanoma (19)(20)(21).…”

“…Although the multifaceted biological properties and actions of Gal 1 (Table 1) are involved in highly important processes at the molecular and cellular levels in epithelial and nonepithelial tissues (11)(12)(13), the immunoreactivity for this galectin in keratinocytes of normal human adult interfollicular epidermis (NHAIE) still remains in dispute, whereas that of epidermal melanocytes has drawn very little attention so far. This prompted us to investigate the expression of Gal 1 in keratinocytes and melanocytes of NHAIE.…”

Plump endothelial cells integrated into pre-existing venules contribute to the formation of ‘mother’ and ‘daughter’ vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8

“…Gal-1 is a prototypic member of the galectin family with a conserved carbohydrate recognition domain (CRD) that has affinity for multiple N-acetyllactosamine (LacNAc) disaccharides (Gal-GlNAc) present in N- and O-linked glycans. 35 – 38 By association of their monomers, it can form homodimers through its C-terminal domain on the cell surface and in the extracellular space, which results in the formation of molecular complexes. 35 – 38 This lectin participates in signalling pathways, regulating a variety of important biological responses including cell growth, proliferation, cell–cell and cell–matrix adhesion, cell differentiation, motility and cell death, and plays a critical role in the initiation and resolution of the inflammatory response, angiogenesis, fibrosis, and tumour development.…”

“… 35 – 38 This lectin participates in signalling pathways, regulating a variety of important biological responses including cell growth, proliferation, cell–cell and cell–matrix adhesion, cell differentiation, motility and cell death, and plays a critical role in the initiation and resolution of the inflammatory response, angiogenesis, fibrosis, and tumour development. 35 – 38 Gal-3 is a chimera type galectin that is composed of a C-terminal domain that binds to specific N- and O-glycan ligands, and an N-terminal domain which facilitates its multidimerisation and generation of galectin–glycan (gal–glycan) lattices on the cell membrane and in the extracellular space controlling several cellular processes through specific signalling pathways; those processes include cell–cell adhesion, cell–matrix adhesion, proliferation, growth, differentiation, migration, inflammation, immune response, apoptosis, angiogenesis and tumour development. 39 – 45 It is predominantly localised in the cytoplasm but can also be detected in the nucleus, intracellular and extracellular sides of the cell membrane, and found in the extracellular space.…”

Galectin‐1 production is elevated in hypertrophic scar

“…Gal‐1 contains six cysteine residues, and its activity is thus sensitive to the redox state of its environment; oxidized Gal‐1 appears to have reduced lectin activity and may have increased cytokine‐like behavior 11 . In the skin, Gal‐1 is expressed in the cytoplasm of keratinocytes and melanocytes of the epidermis, and in dermal fibroblasts and endothelial cells, as well as in hair follicles and the ECM of the dermis 6,12 . Reactive oxygen species (ROS) scavengers are downregulated in the skin during HTS development which likely affects the oxidation state and activity of Gal‐1 13 …”