Effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in pulmonary fibrosis rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

MU Mao ,  CHENG Deyun , YANG Liteng , FANG Xun , NIE Li , HU Xiaobo

Department of Respiratory Medicine，West China Hospital，Sichuan University.Chengdu，Sichuan，610041，China.Corresponding Author：CHENG De-yun，E-mail：chengdeyun@sohu.com;

Corresponding author：

CHENG Deyun, Email: chengdeyun@sohu.com

Keywords：

Pulmonary fibrosis; Sodium ferulate; Transforming growth factor-β1

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Objective To investigate the effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in rats with pulmonary fibrosis，and explore the mechanism of sodium ferulate on pulmonary fibrosis.Methods A rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin (5 mg/kg).Thirty SD rats were randomly divided into three groups (n=10 in each group)，ie.a control group，a pulmonary fibrosis model group，and a sodium ferulate group.The lung histopathology and the expression of collagen was examined by HE staining and collagen fibril staining respectively.The expressions of TGF-βRII and Smad4 mRNA in the lung tissue were detected by situ hybridization.And the expression of TGF-β1 mRNA was detected by real-time fluorescence-quantification RT-PCR.Results Collagen fibril staining indicated that the expression of pulmonary collagen in the model group was significantly higher than that in the control group and sodium ferulate group (P lt;0.001).The mRNA expressions of pulmonary TGF-β1，TGF-βRII and Smad4 were significantly higher in the model group than those in the control group (all P lt;0.01)，and were significantly lower in the sodium ferulate group than those in the model group (all P lt;0.05).Conclusions Sodium ferulate can effectively reduce pulmonary fibrosis through inhibition of the mRNA expression of TGF-β1，TGF-βRII and Smad4 in the lung tissue，thus influence the TGF-β1/Smad4 signal transduction way and inhibit the target gene activation.

Citation： MU Mao,CHENG Deyun,YANG Liteng,FANG Xun,NIE Li,HU Xiaobo. Effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in pulmonary fibrosis rats. Chinese Journal of Respiratory and Critical Care Medicine, 2007, 6(2): 110-113. doi: Copy

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11.	Xaubet A，Marin-Arguedas A，Lario S，et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med，2003，168：431-435.
12.	Bartram U，Speer CP.The role of transforming growth factor beta in lung development and disease.Chest，2004，125：754-765.
13.	Wrana JL，Attisano L，Wieser R，et al.Mechanism of activation of the TGF-beta receptor.Nature，1994，370：341-347.
14.	Heldin CH，Miyazono K，ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature，1997，390：465-471.
15.	Correia JJ，Chacko BM，Lam SS，et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3：Smad4 homo- and hetero-trimerization.Biochemistry，2001，40：1473-1482.
16.	廖丹，江建宁.肝纤维化形成的机制——信号转导通路TGF-β/Smad的作用概论.国外医学（流行病学与传染病学分册），2004，31：170-172.
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20.	黄瑾，胡晋红，邱磊，等.阿魏酸钠抑制肝星状细胞合成胶原的机制.药学学报，2004，39：577 -580.

1. Xaubet A，Marin-Arguedas A，Lario S，et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med，2003，168：410-411.
2. 贺德，曾志良，曹建华，等.阿魏酸钠抗大鼠肝纤维化.世界华人消化杂志，2002，10：240-241.
3. 陈辉珍，樊均明.阿魏酸钠与肾间质纤维化关系的探讨.中药新药与临床药理，2003，14：353-355.
4. 王伯沄，李玉松，黄高异，主编.病理学技术.北京：人民卫生出版社，2000：142-144.
5. Weller SA.，Elphinstone JG，Smith NC，et al.Detection of Ralstonia solanacearum strains with a quantitative，multiplex，real-time，fluorogenic PCR (TaqMan) assay.Appl Environ Microbiol，2000，66：2853-2858.
6. Clark JG，Kostal KM，Marino BA.Bleomycin-induced pulmonary fibrosis in hamsters.An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.J Clin Invest，1983，72：2082-2091.
7. 徐钰，高占成，陈彬，等.γ-干扰素转基因表达对不同时期博莱霉素致小鼠肺间质纤维化的作用.中国呼吸与危重监护杂志，2005，4：130-134.
8. 马跃文，侯显明，康健，等.转化生长因子β1及其Ⅰ、Ⅱ型受体在肺纤维化组织中的表达变化和意义.中华结核和呼吸杂志，2000，23：701-702.
9. 徐晓峰，王辰，代华平，等.大鼠肺纤维化过程中转化生长因子β1及其受体的同相表达.中华结核和呼吸杂志，2002，25：550-551.
10. 刘涛，宋良文.肺纤维化发生的分子机制和早期防治研究进展.军事医学科学院院刊，2003，27：312-316.
11. Xaubet A，Marin-Arguedas A，Lario S，et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med，2003，168：431-435.
12. Bartram U，Speer CP.The role of transforming growth factor beta in lung development and disease.Chest，2004，125：754-765.
13. Wrana JL，Attisano L，Wieser R，et al.Mechanism of activation of the TGF-beta receptor.Nature，1994，370：341-347.
14. Heldin CH，Miyazono K，ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature，1997，390：465-471.
15. Correia JJ，Chacko BM，Lam SS，et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3：Smad4 homo- and hetero-trimerization.Biochemistry，2001，40：1473-1482.
16. 廖丹，江建宁.肝纤维化形成的机制——信号转导通路TGF-β/Smad的作用概论.国外医学（流行病学与传染病学分册），2004，31：170-172.
17. Zhang W，Ou J，Inagaki Y，et al.Synergistic cooperation between Spl and Smad3/Smad4 mediates transforming growth factor betal stimulation of alpha2(I)-collagen (COLIA2) transcription.J Biol Chem，2000，275：39237-39245.
18. Ghosh AK，Yuan W，Mori Y，et al.Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth facter-beta.Integration at the level of p300/CBP transcriptional coactivators.J Biol Chem，2001，276：11041-11048.
19. 刘向峰，李娜.阿魏酸钠的临床应用.宁夏医学杂志，2005，27：69-70.
20. 黄瑾，胡晋红，邱磊，等.阿魏酸钠抑制肝星状细胞合成胶原的机制.药学学报，2004，39：577 -580.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in pulmonary fibrosis rats

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