title: The developmentally-regulated Smoc2 gene is repressed by Aryl-hydrocarbon receptor (Ahr) signaling.
abstract: SPARC-Related Modular Calcium Binding Protein-2 (Smoc-2) is a broadly-expressed matricellular protein which contributes to mitogenesis via activation of Integrin-Linked Kinase (ILK). Here we show that expression of Smoc2 is repressed in cultured cells following treatment with Aryl-hydrocarbon receptor (Ahr) ligands including the ubiquitous environmental pollutants Benzo[a]pyrene (B[a]P) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The Smoc2 promoter contains two consensus putative Ahr-binding sites and Smoc2 promoter-driven reporter genes are repressed in response to B[a]P in an Ahr-dependent manner in cultured cells. Using organ culture experiments we show that TCDD also represses Smoc2 mRNA expression in testes from Ahr(+/+) but not Ahr(-/-) mice. Therefore, exposure to Ahr ligands is likely to affect Smoc2 expression in vivo. Taken together our results indicate that Smoc2 is a novel transcriptional target of activated Ahr. Perturbation of Smoc2 expression may mediate the adverse developmental effects of environmental aryl-hydrocarbon exposure.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Peijun
authors.initials: P
authors.lastname: Liu
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Pazin
authors.forename: Rebeka R
authors.initials: RR
authors.lastname: Merson
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Albrecht
authors.forename: Cyrus
authors.initials: C
authors.lastname: Vaziri
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D051379:Mice; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D018336:Receptors, Aryl Hydrocarbon; C513851:SMOC-2 protein, mouse; D001564:Benzo(a)pyrene