title: Expression of pro-fibrotic and anti-fibrotic molecules in dimethylnitrosamine-induced hepatic fibrosis.
abstract: BACKGROUND
  Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors.
  
  
  OBJECTIVE
  To evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice.
  
  
  METHODS
  Chronic hepatitis was induced in 12 Smad3 wild-type (WT) and 12 knock-out (KO) mice by intraperitoneal DMN administration. Histological, morphometric and immunohistochemical analyses using α-smooth muscle actin (α-SMA), collagen types I-III, TGF-β1, Smad3, avβ6 integrin, CTGF, mTOR and PPARγ antibodies were performed.
  
  
  RESULTS
  The liver of DMN-treated Smad3 WT mice showed a higher degree of hepatic accumulation of connective tissue compared to KO mice. The expression of α-SMA, collagen I-III and CTGF was increased in Smad3 WT compared to KO mice treated with DMN, associated with a concomitant up-regulation of avβ6, TGFβ, Smad3, and mTOR and a reduction in PPARγ expression.
  
  
  CONCLUSIONS
  These results suggest a possible interaction between pro-fibrotic and anti-fibrotic molecules in the development of hepatic fibrosis.
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Human Anatomy, University of L'Aquila, Via Vetoio Coppito 2, 67100 L'Aquila, Italy. Electronic address: roberta.sferra@univaq.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sferra
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Human Anatomy, University of L'Aquila, Via Vetoio Coppito 2, 67100 L'Aquila, Italy. Electronic address: antonella.vetuschi@univaq.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Vetuschi
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Human Anatomy, University of L'Aquila, Via Vetoio Coppito 2, 67100 L'Aquila, Italy. Electronic address: pompili.simona@virgilio.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Pompili
authors.affiliation: Department of Anatomical, Histological, Forensic, Medicine and Orthopedic Sciences, Sapienza University of Rome, Via Francesco Borelli, Rome, Italy. Electronic address: eugenio.gaudio@uniroma1.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.affiliation: Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila, Via Vetoio Coppito 2, 67100 L'Aquila, Italy. Electronic address: silviaspeca@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Speca
authors.affiliation: Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila, Via Vetoio Coppito 2, 67100 L'Aquila, Italy. Electronic address: giolatel@tin.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Latella
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D016023:Integrins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C526318:CCN2 protein, mouse; D016023:Integrins; D047495:PPAR gamma; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D004128:Dimethylnitrosamine
keywords: CTGF; Integrins; Liver fibrosis; PPARγ; TGF-β; mTOR