title: Inhibitory effect of bone morphogenetic protein-7 on hepatic fibrosis in rats.
abstract: OBJECTIVE
  Hepatic cirrhosis is a serious clinical problem caused by the accumulation of extracellular matrix, which can ultimately progress into hepatic failure. Transforming growth factor-beta1 (TGF-β1) plays a pivotal role in extracellular matrix production. Bone morphogenetic protein-7 (BMP-7), as a member of the TGF-β1 superfamily, has been well proved to be capable of reversing renal fibrosis in mice. In this study, we aim to investigate the potential effect of BMP-7 on hepatic fibrosis in rats.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into five groups. In the hepatic fibrosis model group (n=8), rats was treated with porcine serum at 0.5 ml each time, twice a week. In the negative control group (n=10), rats were intraperitoneally injected with equal amount and frequency saline. Rats were injected with BMP-7 (100 μg/kg weight) before porcine serum intraperitoneal injection in the preventive group (n=9). For the early (n=10) and late (n=8) treatment group, rats were received with BMP-7 (100 μg/kg weight) every other day since the second and fourth week respectively after porcine serum injection. After eight weeks, the degree of liver fibrosis in rats was evaluated and the expression of TGF-β1 in liver tissues was detected by Western blot and immunohistochemistry.
  
  
  RESULTS
  The grade of hepatic fibrosis was significant attenuated by BMP-7 prevention and treatment compared with the rats in negative control group (P<0.05). In addition, the expression of TGF-β1 greatly decreased in the BMP-7 preventive and treatment groups detected by both Western blot and immunohistochemistry.
  
  
  CONCLUSIONS
  BMP-7 can attenuate and even prevent the level of hepatic fibrosis in rats through inhibiting the expression of TGF-β1 in the liver fibrotic tissues. Therefore, it may be a potential clinical drug for the prevention and treatment of hepatic fibrosis.
authors: Division of Gastroenterology and Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Sheng-Lan
authors: SL
authors: Wang
authors: Chang-Qing
authors: CQ
authors: Yang
authors: Xiao-Long
authors: XL
authors: Qi
authors: Min
authors: M
authors: Yuan
authors: Yi-Zhong
authors: YZ
authors: Chang
authors: Li
authors: L
authors: Yang
authors: Heng-Jun
authors: HJ
authors: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D053773:Transforming Growth Factor beta1
keywords: Hepatic fibrosis; bone morphogenetic protein-7; extracellular matrix; hepatic stellate cell; transforming growth factor-beta 1
references: Dig Dis Sci. 2007 Dec;52(12):3404-15
references: 17415633
references: Am J Physiol Lung Cell Mol Physiol. 2006 Jan;290(1):L120-6
references: 16126788
references: Bone. 1996 Dec;19(6):569-74
references: 8968021
references: Clin Calcium. 2007 Feb;17(2):263-9
references: 17272885
references: J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S1-6
references: 11263660
references: J Immunol. 2003 Mar 1;170(5):2557-63
references: 12594282
references: Hepatology. 2001 Jul;34(1):89-100
references: 11431738
references: Mol Biol Cell. 2005 Apr;16(4):1987-2002
references: 15689496
references: Int J Exp Pathol. 2006 Jun;87(3):197-208
references: 16709228
references: Zhonghua Yi Xue Za Zhi. 2009 Feb 17;89(6):419-22
references: 19567125
references: J Surg Res. 2004 Oct;121(2):159-70
references: 15501455
references: J Neurosci Res. 2005 Mar 1;79(5):608-15
references: 15678513
references: Am J Physiol Cell Physiol. 2006 Jan;290(1):C282-9
references: 16120655
references: J Biol Chem. 2005 Mar 4;280(9):8094-100
references: 15591043
references: World J Gastroenterol. 2002 Oct;8(5):901-7
references: 12378639
references: Mol Cell Biol. 2003 Sep;23(18):6646-61
references: 12944489
references: J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 1):1024-35
references: 18505415
references: J Hepatol. 1999 Jan;30(1):77-87
references: 9927153
references: Kidney Int. 2002 Jan;61(1):51-60
references: 11786084
references: Mol Cell Biol. 2005 Jun;25(11):4703-15
references: 15899872
references: Cancer Surv. 1996;27:41-64
references: 8909794
references: Cold Spring Harb Symp Quant Biol. 1997;62:269-72
references: 9598360
references: Gastroenterology. 2004 Sep;127(3):914-23
references: 15362046
references: J Nephrol. 2009 May-Jun;22(3):403-10
references: 19557718
references: J Biol Chem. 2004 May 28;279(22):23200-6
references: 15047707
references: Med Mol Morphol. 2006 Mar;39(1):16-21
references: 16575510
references: Am J Physiol Renal Physiol. 2003 May;284(5):F1006-13
references: 12676736
references: Nat Med. 2003 Jul;9(7):964-8
references: 12808448
references: Expert Rev Mol Med. 2003 Feb 14;5(5):1-23
references: 14987408
references: J Gastroenterol Hepatol. 2008 Mar;23 Suppl 1:S122-7
references: 18336655