title: Tissue inhibitor of metalloproteases-4 (TIMP-4) modulates adipocyte differentiation in vitro.
abstract: 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-4's role in adipogenesis, microarray expression analyses were performed. Network enrichment analyses uncovered 25 significant upstream signaling pathways, among which the NFκB cascade was found. Previous works have shown that NFκB is a key regulator of adipogenesis. In accordance, we found that TIMP-4 knockdown decreased NFκB activity during adipogenesis. The present work suggests that TIMP-4 might act as a negative regulator of adipogenesis through NFκB cascade modulation.
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: luz.mejiac@gmail.com.
authors.forename: Luz María
authors.initials: LM
authors.lastname: Mejia-Cristobal
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: reus.erika@gmail.com.
authors.forename: Erika
authors.initials: E
authors.lastname: Reus
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: fjlizarraga@inmegen.gob.mx.
authors.forename: Floria
authors.initials: F
authors.lastname: Lizarraga
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: mespinosa@inmegen.gob.mx.
authors.forename: Magali
authors.initials: M
authors.lastname: Espinosa
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: gceballos@inmegen.gob.mx.
authors.forename: Gisela
authors.initials: G
authors.lastname: Ceballos-Cancino
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: tvlopez@inmegen.gob.mx.
authors.forename: Tania V
authors.initials: TV
authors.lastname: López
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: sags789@gmail.com.
authors.forename: Sergio
authors.initials: S
authors.lastname: Garay
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: vmaldonado@inmegen.gob.mx.
authors.forename: Vilma
authors.initials: V
authors.lastname: Maldonado
authors.affiliation: Basic Research Subdirection, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan, Mexico D.F. 14610, Mexico. Electronic address: jmelendez@inmegen.gob.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Melendez-Zajgla
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis; D000818:Animals; D055785:Gene Knockdown Techniques; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology*; D059467:Transcriptome; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D016328:NF-kappa B; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4
keywords: Adipogenesis; NFκB; TIMP-4