title: Thalidomide Accelerates the Degradation of Extracellular Matrix in Rat Hepatic Cirrhosis via Down-Regulation of Transforming Growth Factor-β1.
abstract: OBJECTIVE
  The degradation of the extracellular matrix has been shown to play an important role in the treatment of hepatic cirrhosis. In this study, the effect of thalidomide on the degradation of extracellular matrix was evaluated in a rat model of hepatic cirrhosis.
  
  
  METHODS
  Cirrhosis was induced in Wistar rats by intraperitoneal injection of carbon tetrachloride (CCl₄) three times weekly for 8 weeks. Then CCl₄ was discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks. Serum hyaluronic acid, laminin, procollagen type III, and collagen type IV were examined by using a radioimmunoassay. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-smooth muscle actin (α-SMA) protein in the liver, transforming growth factor β1 (TGF-β1) protein in cytoplasm by using immunohistochemistry and Western blot analysis, and MMP-13, TIMP-1, and TGF-β1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Liver histopathology was significantly better in rats given thalidomide than in the untreated model group. The levels of TIMP-1 and TGF-β1 mRNA and protein expressions were decreased significantly and MMP-13 mRNA and protein in the liver were significantly elevated in the thalidomide-treated group.
  
  
  CONCLUSIONS
  Thalidomide may exert its effects on the regulation of MMP-13 and TIMP-1 via inhibition of the TGF-β1 signaling pathway, which enhances the degradation of extracellular matrix and accelerates the regression of hepatic cirrhosis in rats.
authors.affiliation: Department of Gastroenterology, Jining First People's Hospital, Jining, China. jnlvpeng@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Lv
authors.affiliation: Department of Gastroenterology, Jining First People's Hospital, Jining, China.
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Gastroenterology, Jining First People's Hospital, Jining, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Jining First People's Hospital, Jining, China.
authors.forename: Chuanfang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000199:Actins; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D024061:Collagen Type III / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000187:drug effects*; D015291:Transforming Growth Factors / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024061:Collagen Type III; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D013792:Thalidomide; D015291:Transforming Growth Factors; D002251:Carbon Tetrachloride
keywords: Thalidomide; cirrhosis; extracellular matrix; matrix metalloproteinase-13; tissue inhibitor of metalloproteinase-1; transforming growth factor-β1