Cryptic fragment alpha4 LG4-5 derived from laminin alpha4 chain inhibits de novo adipogenesis by modulating the effect of fibroblast growth factor-2 |
| |
Authors: | Yamashita Hironobu Goto Chie Tajima Rie Koparal Ayse Tansu Kobori Masato Ohki Yuji Shitara Kenya Narita Ryo Toriyama Kazuhiro Torii Shuhei Niimi Tomoaki Kitagawa Yasuo |
| |
Institution: | Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601;;Department of Biology, Faculty of Science, Anadolu University, Eskisehir 26470, Turkey;;BioFrontier Laboratories, Kyowa Hakko Kogyo Co., Ltd, Asahi-cho, Machida 194-8533;;Graduate School of Medicine, Nagoya University, Showa, Nagoya 466-8550, Japan |
| |
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 α 4 chain in various tissues. However, the functional role of this fragment has remained unknown to date. To investigate this, we prepared α 4 LG1-3 and α 4 LG4-5 fragments by elastase digestion of recombinant α 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 α 4 LG1-5 suppressed adipogenesis to some extent, the α 4 LG4-5 fragment could strongly suppress adipogenesis at a concentration of less than 20 n m . Addition of the α 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 α 4 LG4 module, suppressed adipogenesis. Thus, these results suggest that the cryptic α 4 LG4-5 fragment derived from the laminin α 4 chain inhibits de novo adipogenesis by modulating the effect of FGF-2 through syndecans. |
| |
Keywords: | extracellular matrix fibroblast growth factor-2 heparin Matrigel syndecan |
本文献已被 PubMed 等数据库收录! |
|