Galectins-3 and -7, but not Galectin-1, Play a Role in Re-epithelialization of Wounds

Cao, Zhiyi; Said, Neveen; Amin, Shalin; Wu, Helen; Bruce, Amenda; Gárate, Marco; Hsu, Daniel K.; Kuwabara, Ichiro; Liu, Fu‐Tong; Panjwani, Noorjahan

doi:10.1074/jbc.m200981200

Cited by 168 publications

(180 citation statements)

References 37 publications

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“…Alternatively, galectin-7 may be secreted through the posodomes, which would be consistent with the recent discovery that these structures are sites of secretion (Linder, 2007). In support of this hypothesis, Cao et al (2002) found that adding exogenous galectin-7 accelerates the rate of healing of wounded cornea. Once externalized, like other members of this gene family, galectin-7 might function as a matricellular molecule modulating adhesion, for example by regulating interactions between integrins and ECM components and/or by rapidly remodelling local ECM (Hikita et al, 2000;Levy et al, 2001;Elola et al, 2007).…”

Section: Discussionsupporting

confidence: 72%

“…Several lines of evidence indirectly suggested that galectin-7 might play a role in epithelial tissue response to environmental stimuli. First, galectin-7 could intervene in the process of wound-healing because it is up-regulated in wounded cornea (Cao et al, 2003) and addition of the recombinant protein accelerates the speed of healing in culture (Cao et al, 2002). Second, galectin-7 has been described as a proapoptotic factor involved in the epidermal response after UVB injury.…”

Section: Introductionmentioning

confidence: 99%

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Galectin-7 in the Control of Epidermal Homeostasis after Injury

Gendronneau

Sidhu

Delacour

et al. 2008

MBoC

105

131

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Galectins, a family of ␤-galactoside binding lectins, have recently emerged as novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in stratified epithelia, especially in epidermis. We report here the generation of galectin-7-deficient mice that are viable and do not display phenotypical abnormalities in skin structure or expression of epidermal markers. However, these mice show unique defects in the maintenance of epidermal homeostasis in response to environmental challenges. First, after UVB irradiation in vivo, the apoptotic response is prematurely triggered and lasts longer in the mutant epidermis. This result contrasts with the proapoptotic role that had been proposed for galectin-7. Second, wound-healing experiments in vivo revealed that galectin-7-deficient mice displayed a reduced reepithelialization potential compared with wild-type littermates. This effect could be attributed to a defect in cell migration. Because galectin-7 is located in the podosomes of keratinocytes migrating out of skin explants in culture, we propose that this glycan-binding protein may directly influence cell/extracellular matrix interactions. Finally, we also detected an unexpected intense hyperproliferative reaction consecutive to both types of stress in galectin-7-deficient mice. Together, these studies provide the first genetic evidence showing that galectin-7 can modulate keratinocyte apoptosis, proliferation, and migration during skin repair. INTRODUCTIONGalectins are a family of soluble lectins sharing a unique carbohydrate recognition domain (CRD) that confers specificity for ␤-galactoside derivatives (Barondes et al., 1994a,b). The 15 mammalian members known to date can be classified into three groups on the basis of their structure, namely, "proto-type" galectins containing one CRD domain (14 kDa); galectin-3 (30 kDa), which is a unique chimeric molecule containing a single CRD motif combined with a prolinerich N-terminal domain; and tandem-repeat galectins that are composed of two CRDs separated by a short linker sequence (30 kDa) (Hirabayashi and Kasai, 1993). Despite their lack of signal peptide, galectins can be secreted by an endoplasmic reticulum (ER)-Golgi-independent pathway (Lindstedt et al., 1993;Sato et al., 1993). They can be found both intracellularly (cytoplasm and/or nucleus) and extracellularly depending on the cell type, cell cycle stage, and differentiation state. Galectins can be associated with the plasma membrane, but they do not contain transmembrane domain. Consistent with this variable subcellular location, galectins have been implicated in a wide range of cellular processes, including cell-cell interactions, extracellular matrix remodelling, apoptosis, the cell cycle, intracellular trafficking, and splicing (Hughes, 2001;Liu et al., 2002;Hsu and Liu, 2004;Delacour et al., 2006;Elola et al., 2007). Their roles in cancer biology (Lahm et al., 2004;Takenaka et al., 2004;Liu and Rabinovich, 2005;Thijssen et al., 2007), immune response (Sato and Nieminen, 2004;Rabinovich et a...

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Galectin-7 in the Control of Epidermal Homeostasis after Injury

Gendronneau

Sidhu

Delacour

et al. 2008

MBoC

105

131

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“…However, increased cell migration on GnT-IIILm332 was not induced by exogenous galectin-3, because modification of Lm332 by GnT-III reduced its ability to bind to galectin-3. These results strongly suggest that galectin-3 may be a cofactor for Lm332-induced cell motility during wound healing and squamous cell carcinoma tumor progression conditions that are associated with GnT-V overexpression (35,36). Therefore, the opposing galectin functions may be attributed to FIGURE 6.…”

Section: Discussionmentioning

confidence: 96%

“…Cytosolic galectin-3 is involved in the regulation of cell proliferation, differentiation, survival, and death (33). Galectin-3 is highly expressed in some cancers, including the human skin cancer squamous cell carcinoma (34,35), and at the leading edge of wound sites (36). Galectin-3 forms a lattice or cell surface microdomain, which links cytokine receptors on the cell surface (37).…”

mentioning

confidence: 99%

Bisecting GlcNAc Residues on Laminin-332 Down-regulate Galectin-3-dependent Keratinocyte Motility

Kariya

Kawamura

Tabei

et al. 2010

Journal of Biological Chemistry

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(2008) J. Biol. Chem. 283, 33036 -33045). However, the underlying molecular mechanism by which GnT-III-Lm332 suppresses the normal biological functions of Lm332 remains to be elucidated. In this study, we show that galectin-3, which is a ␤-galactoside-binding protein, strongly bound to unmodified Lm332 but not to GnT-IIILm332 and that binding of galectin-3 was completely blocked by lactose. Exogenous galectin-3 significantly enhanced keratinocyte cell motility on control Lm332 but not on GnT-III-Lm332. A functional blocking antibody against galectin-3 inhibited Lm332-induced ␣3␤1 and ␣6␤4 integrin clustering and focal contact formation. Co-immunoprecipitation revealed that galectin-3 associated with both ␤4 integrin and epidermal growth factor receptor, thereby cross-linking the two molecules. The associations were inhibited by either the presence of lactose or expression of GnT-III. Moreover, galectin-3 consistently enhanced ERK activation. Taken together, the results of this study are the first to clearly identify the molecular mechanism responsible for the inhibitory effects of GnT-III on extracellular matrix-integrin-meditated cell adhesion, migration, and signal transduction. The findings presented herein shed light on the importance of N-glycosylation-mediated supramolecular complex formation on the cell surface.Tissue maintenance requires that cells be in communication with the surrounding microenvironment. During both physical and pathological conditions, cells receive extracellular matrix (ECM) 2 -mediated signals via cell surface receptors, including cell adhesion, migration, differentiation, and proliferation (1, 2). Significant research effort, using biochemical and genetic techniques, has advanced our understanding of how ECM signals are transduced and then translated into the cell. However, most studies have focused on the protein-protein interactions, namely on ECM-cell surface receptor interactions, rather than on carbohydrate-protein interactions.Laminin-332 (Lm332; previously known as laminin-5) is a component of basement membranes in the skin and other stratified squamous epithelial tissues (2-4). Lm332, which consists of ␣3, ␤3, and ␥2 subunits, associates with hemidesmosomes through integrin ␣6␤4 (5). A null mutation for Lm332 causes a severe and lethal skin blistering disease (6, 7). On the other hand, Lm332 is overexpressed at the leading edge of wounds during healing (8 -10) and in various types of squamous and other epithelial tumors (11,12). In addition, Lm332 plays an essential role in a mouse model of human squamous cell carcinoma tumorigenesis (13). Consistent with the result of in vivo studies, Lm332 promotes various cellular activities in vitro, such as cell adhesion, spreading, migration, and proliferation, via association of the carboxyl-terminal globular domain of the ␣3 chain with cell surface receptors, such as ␣3␤1 integrin, ␣6␤4 integrin, and syndecans (14 -16).Although between 13 and 30% of the total molecular weight of laminins is N-linked glycosylated (17), most studies o...

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“…The findings that (i) galectin-3 expression, e.g., in placenta, 54 epithelium of the tongue 55 and keratinocytes, 56 correlates with C4.4A expression and that (ii) galectin-3 57 and C4.4A become upregulated during wound healing 48 point toward functional relevance of the C4.4A-galectin-3 association in supporting cell migration. Galectin-3 is found on the plasma membrane, in the cytosol and in the nucleus.…”

Section: C44a Associates With Galectin-3mentioning

confidence: 95%

Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin‐3 and supports cell migration

Paret

Bourouba

et al. 2005

Intl Journal of Cancer

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C4.4A is a member of the Ly6 family, with low homology to uPAR. It has been detected mainly on metastasizing carcinoma cells and proposed to be involved in wound healing. So far, C4.4A has been observed as an orphan receptor, and its functional activity has not been explored. Using recombinant rat C4.4A (rrC4.4A) made in a eukaryotic expression system, we demonstrate by immunohistology that C4.4A ligands are strongly expressed in tissues adjacent to squamous epithelia of, e.g., tongue and esophagus, the expression pattern partly overlapping with laminin (LN) and complementing the C4.4A expression that is found predominantly on the basal layers of squamous epithelium. ELISA screening of several components of the extracellular matrix revealed selective binding of rrC4.4A to LN1 and LN5 and that transfection of the BSp73AS tumor line with C4.4A cDNA (BSp73AS-1B1) promoted LN1 and LN5 binding. Binding of BSp73AS-1B1 to LN5 and, less markedly, LN1 induced spreading, lamellipodia formation and migration. C4.4A also associates with galectin-3 in nontransformed tissues and tumor lines. There is evidence that the association of C4.4A with galectin-3 influences LN adhesion. C4.4A was described originally as a metastasis-associated molecule. Our findings that LN1 and LN5 are C4.4A ligands, that galectin-3 associates with C4.4A and that C4.4A ligand binding confers a migratory phenotype are well in line with the supposed metastasis association. ' 2005 Wiley-Liss, Inc.Key words: C4.4A; laminin; galectin; cell migration LNs are adhesive glycoproteins found in the basement membrane. Fifteen LN isoforms have been identified. 1 LN isoforms are tissue-specific and expressed in a developmentally regulated pattern. 2,3 Cell adhesion to LN plays an important role in maintaining normal tissue organization. LNs promote cell adhesion and migration, 4 are involved in the control of cell proliferation and gene expression 5 and stimulate neurite outgrowth, 6 the multitude of functions being brought about by a large array of receptors. 7 The most prominent LN receptors are integrins, but distinct receptors have also been described, e.g., a-dystroglycan, syndecans, the 67 kDa LN receptor and galectins. 7,8 a-Dystroglycan provides a link between the basement membrane and the dystrophin-actin cytoskeleton. 9 Its binding to LN is Ca 2þ -dependent 10 and requires carbohydrate moieties. 11 Binding of syndecans 2 and 4 to LN5 induces expression of MMP-1. 12 Moreover, syndecan 1 interacts with unprocessed LN5 in migrating keratinocytes, and this interaction depends on the presence of the glycosaminoglycan chain. 13 Galectins belong to the family of galactose-specific lectins and bind the lactosamine-type sugars on LN1. 8 However, at high concentrations, galectins 3 and 1 can downregulate adhesion to LN, probably by blocking the cellular attachment sites. 14,15 The 67 kDa LN receptor can act in concert with a6b4 to promote cell adhesion to LN1. 16 It is also involved in the degradation of LN1 and the release of motility fragments. 17 The GPI-ancho...

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Galectins-3 and -7, but not Galectin-1, Play a Role in Re-epithelialization of Wounds

Cited by 168 publications

References 37 publications

Galectin-7 in the Control of Epidermal Homeostasis after Injury

Galectin-7 in the Control of Epidermal Homeostasis after Injury

Bisecting GlcNAc Residues on Laminin-332 Down-regulate Galectin-3-dependent Keratinocyte Motility

Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin‐3 and supports cell migration

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