First Author | Mejia-Cristobal LM | Year | 2015 |
Journal | Exp Cell Res | Volume | 335 |
Issue | 2 | Pages | 207-15 |
PubMed ID | 25999146 | Mgi Jnum | J:221947 |
Mgi Id | MGI:5643784 | Doi | 10.1016/j.yexcr.2015.05.006 |
Citation | Mejia-Cristobal LM, et al. (2015) Tissue inhibitor of metalloproteases-4 (TIMP-4) modulates adipocyte differentiation in vitro. Exp Cell Res 335(2):207-15 |
abstractText | Tissue inhibitors of metalloproteases (TIMPs) are multifunctional proteins that inhibit matrix metalloproteases (MMPs). The latest described member of the family, TIMP-4, is expressed mainly in adipose tissue, with detectable levels in the brain and heart. Besides its high expression in fat, the role of this inhibitor in adipose tissue is unknown. In order to study the role of TIMP-4 during adipogenesis in vitro, 3T3-L1 cells were stably transfected with a TIMP-4 specific shRNA or a control shRNA. Unexpectedly, upon TIMP-4 knockdown, 3T3-L1 cells differentiated faster into mature adipocytes. To get better insight of TIMP-4s role in adipogenesis, microarray expression analyses were performed. Network enrichment analyses uncovered 25 significant upstream signaling pathways, among which the NFkappaB cascade was found. Previous works have shown that NFkappaB is a key regulator of adipogenesis. In accordance, we found that TIMP-4 knockdown decreased NFkappaB activity during adipogenesis. The present work suggests that TIMP-4 might act as a negative regulator of adipogenesis through NFkappaB cascade modulation. |