title: A fibronectin-independent mechanism of collagen fibrillogenesis in adult liver remodeling.
abstract: OBJECTIVE
  Fibrosis is an abnormal extension of the wound healing process that follows tissue damage; it is involved in pathogenesis in a variety of chronic diseases. The formation of extracellular matrix is an essential response in wound healing. Although it has been proposed that collagen organization and assembly depend on the fibronectin matrix in culture, the contribution of fibronectin to these processes remains to be defined in vivo.
  
  
  METHODS
  We generated a conditional, fibronectin-deficient mouse model of liver injury and explored whether fibronectin would be a suitable target for preventing extensive collagen deposits and scar formation that could lead to liver fibrosis.
  
  
  RESULTS
  The lack of fibronectin did not interfere with reconstruction of collagen fibril organization in response to liver injury. Signaling by transforming growth factor-β and type V collagen were required for collagen fibrillogenesis during remodeling of adult liver tissue.
  
  
  CONCLUSIONS
  Transforming growth factor-β and type V collagen are targets for regulating the initial fibrogenic response to liver damage.
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: Kei
authors.initials: K
authors.lastname: Moriya
authors.forename: Eunnyung
authors.initials: E
authors.lastname: Bae
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Honda
authors.forename: Keiko
authors.initials: K
authors.lastname: Sakai
authors.forename: Takehisa
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Tsujimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamisoyama
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Takao
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002784:Cholesterol / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D005353:Fibronectins; C497045:Npc2 protein, mouse; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D002784:Cholesterol