Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MFAP4 is an integrin M-NM-1VM-NM-23/5 ligand involved in vascular remodeling

ABSTRACT: Arterial injury or occlusive arterial disease may stimulate healing responses, which when overexuberant, leads to restenosis of the injured vessel. This response is influenced by specific integrin signalling in vascular smooth muscle cells (VSMCs). Microfibril-associated protein 4 (MFAP4) colocates in blood vessels with elastic fibers. MFAP4 contains an N-terminal RGD-motiv, which is a potential integrin binding site. The role for MFAP4 in vascularproliferative disease is so far unknown and the subject for these investigations. Here we show that MFAP4 is expressed and secreted by VSMCs and binds elastin and collagen. MFAP4 mediated adhesion, and migration, and proliferation of VSMCs in an integrin M-NM-1VM-NM-23/5 dependent manner and the effects were inhibited by MFAP4 blocking antibodies. MFAP4 deficient mutant mice were generated and appeared with a normal cardiophysiological phenotype. When challenged by carotid artery ligation, the MFAP4 deficient mice had delayed neointimal formation and the compensatory outward remodeling of the vessel diameter and thus the vessel lumen was reduced. MFAP4 expression appeared unaffected by the induced pathology. HUMANE DATA This new MFAP4 mediated molecular mechanism for regulation of integrin M-NM-1VM-NM-23/5 signalling may have therapeutic implications in diseases where VSMC migration and proliferation are involved in the pathogenesis. For genome-wide expression analysis total RNA from heart of four male MFAP4-/- and four control mice was isolated using RNeasy Midi kit (Qiagen, Hilden, Germany). The cDNA microarrays were generated, hybridized and analysed as described (Horsch et al 2009). Two chip hybridizations were performed with total RNA for each individual mutant mouse against a reference RNA pool of the same organ.

ORGANISM(S): Mus musculus

SUBMITTER: Marion Horsch

PROVIDER: E-GEOD-40480 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MFAP4 is an integrin M-NM-1VM-NM-23/5 ligand involved in vascular remodeling

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