Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 425, Issue 2, Pages 390-392Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.07.106
Keywords
Nephronectin; Alk5; SMAD
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24592817, 24791985, 23592748, 23390426, 24592813, 24659830] Funding Source: KAKEN
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Nephronectin (Npnt) is an extracellular matrix protein known to be a ligand for the integrin alpha 8 beta 1. We previously demonstrated that Npnt expression was suppressed by TGF-beta through ERK1/2 and JNK in osteoblasts. In this study, we found that inhibition of a TGF-beta type I receptor (TGF-beta 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-beta, signaling. These results suggest that the expression of Npnt is regulated by the Alk5-SMAD signaling pathway in osteoblasts. (c) 2012 Elsevier Inc. All rights reserved.
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