Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/60798
Title: The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells
Author: Sorianello, E.
Zaragoza, Francesc X. (Francesc Xavier)
Fernández Pascual, S.
Sancho Medina, Ana
Naón Elbirt, Déborah P.
Vila Caballer, M.
González Navarro, H.
Portugal, José, 1954-
Andrés García, Vicente
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
Keywords: Metabolisme cel·lular
Transcripció genètica
Proteïnes
Malalties cardiovasculars
Cell metabolism
Genetic transcription
Proteins
Cardiovascular diseases
Issue Date: 1-Apr-2012
Publisher: Oxford University Press
Abstract: AIMS: Mitofusin-2 (Mfn2) expression is dysregulated in vascular proliferative disorders and its overexpression attenuates the proliferation of vascular smooth muscle cells (VSMCs) and neointimal lesion development after balloon angioplasty. We sought to gain insight into the mechanisms that control Mfn2 expression in VSMCs. METHODS AND RESULTS: We cloned and characterized 2 kb of the 5'-flanking region of the human Mfn2 gene. Its TATA-less promoter contains a CpG island. In keeping with this, 5'-rapid amplification of cDNA ends revealed six transcriptional start sites (TSSs), of which TSS2 and TSS5 were the most frequently used. The strong CpG island was found to be non-methylated under conditions characterized by large differences in Mfn2 gene expression. The proximal Mfn2 promoter contains six putative Sp1 motifs. Sp1 binds to the Mfn2 promoter and its overexpression activates the Mfn2 promoter in VSMCs. Chemical inhibition of Sp1 reduced Mfn2 expression, and Sp1 silencing reduced transcriptional activity of the Mfn2 promoter. In keeping with this view, Sp1 and Mfn2 mRNA levels were down-regulated in the aorta early after an atherogenic diet in apolipoprotein E-knockout mice or in VSMCs cultured in the presence of low serum. CONCLUSION: Sp1 is a key factor in maintaining basal Mfn2 transcription in VSMCs. Given the anti-proliferative actions of Mfn2, Sp1-induced Mfn2 transcription may represent a mechanism for prevention of VSMC proliferation and neointimal lesion and development.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1093/cvr/cvs006
It is part of: Cardiovascular Research, 2012, vol. 94, num. 1, p. 38-47
Related resource: http://dx.doi.org/10.1093/cvr/cvs006
URI: http://hdl.handle.net/2445/60798
ISSN: 0008-6363
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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