title: Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration.
abstract: Collagen triple helix repeat containing 1 (Cthrc1) was identified in a screen for differentially expressed sequences in balloon-injured versus normal arteries. Cthrc1 expression was not detectable in normal arteries. However, on injury it was transiently expressed by fibroblasts of the remodeling adventitia and by smooth muscle cells of the neointima. It was also found in the matrix of calcifying human atherosclerotic plaques. CTHRC1 is a secreted 28-kDa protein that is glycosylated and highly conserved from lower chordates to mammals. A short collagen motif with 12 Gly-X-Y repeats appears to be responsible for trimerization of the protein and this renders the molecule susceptible to cleavage by collagenase. Cthrc1 mRNA expression levels are increased in response to transforming growth factor-beta and bone morphogenetic protein-4. Cell migration assays performed with CTHRC1-overexpressing fibroblasts and smooth muscle cells demonstrate that increased CTHRC1 levels are associated with enhanced migratory ability. Furthermore, CTHRC1 overexpression caused a dramatic reduction in collagen type I mRNA and protein levels. Our data indicate that the novel molecule CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough 04074, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pyagay
authors.forename: Mélanie
authors.initials: M
authors.lastname: Heroult
authors.forename: Qiaozeng
authors.initials: Q
authors.lastname: Wang
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lehnert
authors.forename: John
authors.initials: J
authors.lastname: Belden
authors.forename: Lucy
authors.initials: L
authors.lastname: Liaw
authors.forename: Robert E
authors.initials: RE
authors.lastname: Friesel
authors.forename: Volkhard
authors.initials: V
authors.lastname: Lindner
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism*; D001704:Biopolymers; D016466:CHO Cells; D002114:Calcinosis / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016893:Carotid Stenosis / Q000209:etiology; D002404:Catheterization / Q000009:adverse effects; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D017364:Collagenases / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000502:physiology; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism
chemical_list: D001704:Biopolymers; C502426:CTHRC1 protein, human; C502427:Cthrc1 protein, rat; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D017364:Collagenases