PMID:24503541

Citation	Yun, SP, Lee, SJ, Jung, YH and Han, HJ (2014) Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression. Cell Death Dis 5:e1049
Abstract	Galectin-1 (Gal-1) belongs to a family of endogenous lectins with conserved carbohydrate recognition domains binding β-galactosidase sugars and plays a vital role in regulating stem cell functions including determination of cell fate. However, our understanding of the functional roles of Gal-1 in human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is still fragmentary and incomplete. Gal-1 significantly increased motility after a 24-h incubation, and this effect was inhibited by β-lactose. We analyzed 17 extracellular matrix (ECM) genes in UCB-MSCs. Gal-1 decreased the expression of collagen genes COL3A1 (COL-3) and COL5A1 (COL-5) but increased the expression of fibronectin (FN) and laminin 5 (LM-5), that were reversed by β-lactose. Gal-1 increased protein kinase C (PKC), c-Src, and caveolin-1 (Cav-1) phosphorylation that was attenuated by β-lactose and the Src inhibitor PP2. In addition, pretreatment with the lipid raft disruptor Mβ-CD and the PKC inhibitors inhibited Gal-1-induced UCB-MSC motility. In addition, Gal-1 reduced smad2/3 phosphorylation and induced nuclear factor (NF)-κB phosphorylation. Pretreatment with Mβ-CD attenuated Gal-1-reduced smad2/3 phosphorylation, COL-3, and COL-5 expression but did not affect NF-κB phosphorylation, FN, or LM-5 expression. In contrast, PKC inhibitors only attenuated NF-κB phosphorylation, FN, and LM-5 expression. Reconstructing Gal-1-induced genetic changes by replacing it with siRNA specific for COL-3 or COL-5, or treatment of the cells with FN and LM-5 proteins, increased motility and its related proteins such as focal adhesion kinase, Akt, Erk, integrins, and matrix metalloproteinase-2. A combined treatment with COL-3/COL-5 siRNA or FN/LM-5 compared with that of single treatments was synergistic. However, a single Gal-1 treatment maximally stimulated motility and related protein phosphorylation/expression. These results demonstrate that Gal-1 stimulated human UCB-MSC motility by decreasing COL-3/COL-5 expression and increasing FN/LM-5 expression through a PKC-dependent NF-κB and c-Src/Cav-1-dependent smad2/3 pathway that was critical for governing the activation of FAK, Akt, Erk, integrins, and MMP2.
Links	PubMed PMC3944255 Online version:10.1038/cddis.2014.3
Keywords	Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cell Movement; Cells, Cultured; Collagen Type III/genetics; Collagen Type III/metabolism; Collagen Type V/genetics; Collagen Type V/metabolism; Down-Regulation; Fetal Blood/cytology; Fetal Blood/metabolism; Fibronectins/genetics; Fibronectins/metabolism; Galectin 1/genetics; Galectin 1/metabolism; Humans; Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism; NF-kappa B/genetics; NF-kappa B/metabolism; Smad2 Protein/genetics; Smad2 Protein/metabolism; Smad3 Protein/genetics; Smad3 Protein/metabolism; Up-Regulation
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:O75079		GO:2000147: positive regulation of cell motility	ECO:0000314:		P		Figure 7 shows Laminin 5 combination with fibronectin stimulating the cell motility of human umbilical cord blood-derived mesenchymal stem cells	complete CACAO 10343
HUMAN:O75079	involved_in	GO:2000147: positive regulation of cell motility	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

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