title: Nephronectin expression is regulated by SMAD signaling in osteoblast-like MC3T3-E1 cells.
abstract: Nephronectin (Npnt) is an extracellular matrix protein known to be a ligand for the integrin α8β1. We previously demonstrated that Npnt expression was suppressed by TGF-β through ERK1/2 and JNK in osteoblasts. In this study, we found that inhibition of a TGF-β type I receptor (TGF-β R1, Alk5) by a specific inhibitor {2-[3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine} strongly induced Npnt expression in osteoblast-like MC3T3-E1 cells. The Alk5 inhibitor-induced increase of Npnt expression occurred in both time- and dose-dependent manners, while that expression was also induced by introduction of an siRNA for Smad2, a central intracellular mediator of TGF-β signaling. These results suggest that the expression of Npnt is regulated by the Alk5-SMAD signaling pathway in osteoblasts.
authors: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Tsukasaki
authors: Atsushi
authors: A
authors: Yamada
authors: Kentaro
authors: K
authors: Yoshimura
authors: Agasa
authors: A
authors: Miyazono
authors: Matsuo
authors: M
authors: Yamamoto
authors: Masamichi
authors: M
authors: Takami
authors: Yoichi
authors: Y
authors: Miyamoto
authors: Naoko
authors: N
authors: Morimura
authors: Ryutaro
authors: R
authors: Kamijo
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology
chemical_list: D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; C432915:nephronectin; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse