Effect of Danshao Huaxian capsule on Gremlin and bone morphogenetic protein-7 expression in hepatic fibrosis in rats.

Abstract

AIM:

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).

CONCLUSION:

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: Xue-Ke Zhao, Ming-Liang Cheng, Rong-Min Wu, Yu-Mei Yao, Mao Mu, Juan-Juan Zhu, Bao-Fang Zhang, Ming-Yu Zhou
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 40 Pg. 14875-83 (Oct 28 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25356047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bmp7 protein, rat
• Bone Morphogenetic Protein 7
• Cytokines
• Drugs, Chinese Herbal
• Grem1 protein, rat
• Proteins
• RNA, Messenger
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• dan-shao-hua-xian
• Carbon Tetrachloride

Topics

• Animals
• Bone Morphogenetic Protein 7 (genetics, metabolism)
• Carbon Tetrachloride
• Chemical and Drug Induced Liver Injury (diagnosis, drug therapy, etiology, genetics, metabolism)
• Cytokines
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Experimental (chemically induced, diagnosis, drug therapy, genetics, metabolism)
• Male
• Proteins (genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats, Wistar
• Severity of Illness Index
• Signal Transduction (drug effects)
• Time Factors
• Transforming Growth Factor beta1 (genetics, metabolism)