title: Effect of Danshao Huaxian capsule on Gremlin and bone morphogenetic protein-7 expression in hepatic fibrosis in rats.
abstract: OBJECTIVE
  To observe the effect of Danshao Huaxian capsule (DHC) on the expression of Gremlin and bone morphogenetic protein-7 (BMP-7) in the liver of hepatic fibrosis rats.
  
  
  METHODS
  A total of 75 male Wistar rats were randomly divided into a normal control group (A), a CCl₄-induced hepatic fibrosis model group (B), a natural recovery group (C), a low-dose DHC-treated group (D), and a high-dose DHC-treated group (E), with 15 rats in each group. Liver fibrosis was induced by subcutaneous injections of carbon tetrachloride (CCl4) and a high-lipid/low-protein diet for 8 wk, except for the rats in group A. Then, the rats in the two DHC-treated groups were administered 0.5 and 1.0 g/kg DHC by gastrogavage once per day for 8 successive weeks, respectively. By the end of the experiment, the level of transforming growth factor β1 (TGF-β1) in the liver homogenate was determined by an enzyme-linked immunosorbent assay. The mRNA and protein expression of Gremlin and BMP-7 in the liver tissue was determined by reverse-transcription polymerase chain reaction, an immunohistochemical assay, and Western blot analysis.
  
  
  RESULTS
  Compared with group A, the level of TGF-β1 and the mRNA and protein expression of Gremlin were significantly higher in group B (TGF-β1: 736.30 ± 24.40 μg/g vs 284.20 ± 18.32 μg/g, P < 0.01; mRNA of Gremlin: 80.40 ± 5.46 vs 49.83 ± 4.20, P < 0.01; positive protein expression rate of Gremlin: 38.46% ± 1.70% vs 3.83% ± 0.88%, P < 0.01; relative protein expression of Gremlin: 2.81 ± 0.24 vs 0.24 ± 0.06, P < 0.01), and the mRNA and protein expression of BMP-7 was significantly lower in group B (mRNA: 54.00 ± 4.34 vs 93.99 ± 7.03, P < 0.01; positive protein expression rate: 28.97% ± 3.14% vs 58.29% ± 6.02, P < 0.01; relative protein expression: 0.48 ± 0.31 vs 1.05 ± 0.12, P < 0.01). Compared with groups B and C, the degree of hepatic fibrosis was significantly improved, and the level of TGF-β1 and the mRNA and protein expression of Gremlin were significantly lowered in the two DHC-treated groups (TGF-β1: 523.14 ± 21.29 μg/g, 441.86 ± 23.18 μg/g vs 736.30 ± 24.40 μg/g, 651.13 ± 15.75 μg/g, P < 0.01; mRNA of Gremlin: 64.86 ± 2.83, 55.82 ± 5.39 vs 80.40 ± 5.46, 70.37 ± 4.01, P < 0.01; positive protein expression rate of Gremlin: 20.78% ± 1.60%, 17.43% ± 2.02% vs 38.46% ± 1.70%, 29.50% ± 2.64%, P < 0.01; relative protein expression of Gremlin: 1.95 ± 0.26, 1.65 ± 0.20 vs 2.81 ± 0.24, 2.22 ± 0.63, P < 0.01), and the mRNA and protein expression of BMP-7 was higher in the two DHC-treated groups (mRNA: 73.52 ± 4.56, 81.78 ± 5.38 vs 54.00 ± 4.34, 62.28 ± 4.51, P < 0.01; positive protein expression rate: 41.44% ± 4.77%, 47.49% ± 4.59% vs 28.97% ± 3.14%, 35.85% ± 3.50%, P < 0.01; relative protein expression: 0.71 ± 0.06, 0.81 ± 0.07 vs 0.48 ± 0.31, 0.60 ± 0.37, P < 0.01).
  
  
  CONCLUSIONS
  The therapeutic mechanism of DHC for hepatic fibrosis in rats may be associated with inhibition of the expression of Gremlin and up-regulation of the expression of BMP-7.
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Rong-Min
authors.initials: RM
authors.lastname: Wu
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Yao
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Mu
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Zhu
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Bao-Fang
authors.initials: BF
authors.lastname: Zhang
authors.affiliation: Xue-Ke Zhao, Ming-Liang Cheng, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou, Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou Province, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D016207:Cytokines; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D016207:Cytokines; D004365:Drugs, Chinese Herbal; C107276:Grem1 protein, rat; D011506:Proteins; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C499780:dan-shao-hua-xian; D002251:Carbon Tetrachloride
keywords: Bone morphogenetic protein; Gremlin; Hepatic fibrosis; Traditional Chinese herbs; Transforming growth factor