Cryptic fragment α4 LG4‐5 derived from laminin α4 chain inhibits de novo adipogenesis by modulating the effect of fibroblast growth factor‐2
- 7 December 2007
- journal article
- Published by Wiley in Development, Growth & Differentiation
- Vol. 50 (2), 97-107
- https://doi.org/10.1111/j.1440-169x.2007.00979.x
Abstract
Cleavage of the extracellular matrix (ECM) by proteolysis unmasks cryptic sites and generates novel fragments with biological activities functionally distinct from those of the intact ECM molecule. The laminin G-like (LG)4-5 fragment has been shown to be excised from the laminin alpha4 chain in various tissues. However, the functional role of this fragment has remained unknown to date. To investigate this, we prepared alpha4 LG1-3 and alpha4 LG4-5 fragments by elastase digestion of recombinant alpha4 LG1-5, and examined their effects on de novo adipogenesis in mice at the site of injection of basement membrane extract (Matrigel) and fibroblast growth factor (FGF)-2. Although the addition of whole alpha4 LG1-5 suppressed adipogenesis to some extent, the alpha4 LG4-5 fragment could strongly suppress adipogenesis at a concentration of less than 20 nm. Addition of the alpha4 LG4 module, which contains a heparin-binding region, had a suppressive effect, but this was lost in mutants with reduced heparin-binding activity. In addition, antibodies against the extracellular domain of syndecan-2 and -4, which are known receptors for the alpha4 LG4 module, suppressed adipogenesis. Thus, these results suggest that the cryptic alpha4 LG4-5 fragment derived from the laminin alpha4 chain inhibits de novo adipogenesis by modulating the effect of FGF-2 through syndecans.Keywords
This publication has 41 references indexed in Scilit:
- The LG1-3 Tandem of Laminin α5 Harbors the Binding Sites of Lutheran/Basal Cell Adhesion Molecule and α3β1/α6β1 IntegrinsPublished by Elsevier BV ,2007
- Crystal Structure and Cell Surface Anchorage Sites of Laminin α1LG4-5Published by Elsevier BV ,2007
- Basic fibroblast growth factor enhances PPARγ ligand‐induced adipogenesis of mesenchymal stem cellsFEBS Letters, 2004
- Molecular Dissection of the α-Dystroglycan- and Integrin-binding Sites within the Globular Domain of Human Laminin-10Published by Elsevier BV ,2004
- Localization of Laminin α4-Chain in Developing and Adult Human TissuesJournal of Histochemistry & Cytochemistry, 2002
- LG/LNS domains: multiple functions – one business end?Trends in Biochemical Sciences, 2001
- Purification and Characterization of Human Laminin-8Published by Elsevier BV ,2001
- High and Low Affinity Heparin-binding Sites in the G Domain of the Mouse Laminin α4 ChainPublished by Elsevier BV ,2000
- Differentiation-dependent expression of laminin-8 (α4β1γ1) mRNAs in mouse 3T3-L1 adipocytesMatrix Biology, 1997
- The complete cDNA coding sequence and tissue-specific expression of the mouse laminin α4 chainMatrix Biology, 1996