Cryptic fragment alpha 4 LG4-5 derived from laminin alpha 4 chain inhibits de novo adipogenesis by modulating the effect of fibroblast growth factor-2

Yamashita H., Goto C., Tajima R., Koparal A. T., Kobori M., Ohki Y., ...Daha Fazla

DEVELOPMENT GROWTH & DIFFERENTIATION, cilt.50, sa.2, ss.97-107, 2008 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 50 Sayı: 2
  • Basım Tarihi: 2008
  • Dergi Adı: DEVELOPMENT GROWTH & DIFFERENTIATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.97-107
  • Anahtar Kelimeler: extracellular matrix, fibroblast growth factor-2, heparin, Matrigel, syndecan, CELL-ADHESION, EXTRACELLULAR-MATRIX, BASEMENT-MEMBRANE, BINDING-SITES, G-DOMAIN, IV COLLAGEN, IN-VIVO, INTEGRINS, CHAIN, HEPARIN
  • Anadolu Üniversitesi Adresli: Evet

Özet

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 alpha 4 chain in various tissues. However, the functional role of this fragment has remained unknown to date. To investigate this, we prepared alpha 4 LG1-3 and alpha 4 LG4-5 fragments by elastase digestion of recombinant alpha 4 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 alpha 4 LG1-5 suppressed adipogenesis to some extent, the alpha 4 LG4-5 fragment could strongly suppress adipogenesis at a concentration of less than 20 nM. Addition of the alpha 4 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 alpha 4 LG4 module, suppressed adipogenesis. Thus, these results suggest that the cryptic alpha 4 LG4-5 fragment derived from the laminin alpha 4 chain inhibits de novo adipogenesis by modulating the effect of FGF-2 through syndecans.