Involvement of 90-kuD ribosomal S6 kinase in collagen type I expression in rat hepatic fibrosis

Miao-Fang Yang; Jun Xie; Xiao-Yi Gu; Xiao-Hua Zhang; Davey, Andrew K.; Shuang-Jie Zhang; Ji-Ping Wang; Ren-Min Zhu; Parola, Maurizio
May 2009
World Journal of Gastroenterology;5/7/2009, Vol. 15 Issue 17, p2109
Academic Journal
AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro. METHODS: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 µg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significant positive correlation with collagen type I levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type I was down-regulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type I promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line (P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type I through initiating the proliferation of HSCs.


Related Articles

  • Pathophysiological Characteristics of Dimethylnitrosamine-Induced Liver Fibrosis in Acute and Chronic Injury Models: A Possible Contribution of KLF5 to Fibrogenic Responses. Aisuke Nii; Yojiro Sakiyama; Megumi Tsuchiya // Digestive Diseases & Sciences;Aug2008, Vol. 53 Issue 8, p2222 

    Abstract  Dimethylnitrosamine administration induces a rapid increase in collagen deposition with concomitant proliferation of hepatic stellate cells in rats. Here, we investigated the pathophysiological profiles of acute and chronic hepatic fibrosis states and attempted to determine the...

  • Preventive effect of Qianggan-Rongxian Decoction on rat liver fibrosis. Chun-Hui Li; Li-Hui Pan; Zong-Wei Yang; Chun-Yu Li; Wen-Xie Xu; Neuberger, James; Shimizu, Yukihiro // World Journal of Gastroenterology;6/14/2008, Vol. 14 Issue 22, p3569 

    AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups (12 rats in each group). Except for the...

  • NDRG2 Ameliorates Hepatic Fibrosis by Inhibiting the TGF-β1/Smad Pathway and Altering the MMP2/TIMP2 Ratio in Rats. Jiandong Yang; Jin Zheng; Lin Wu; Ming Shi; Hongtao Zhang; Xing Wang; Ning Xia; Desheng Wang; Xinping Liu; Libo Yao; Yan Li; Kefeng Dou // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    Liver fibrosis is a worldwide clinical issue. It has been well established that activated hepatic stellate cells (HSCs) are responsible for excessive extracellular matrix (ECM) deposition in chronically damaged livers. The identification of key elements that control HSCs activation will help to...

  • Corrections.  // Gut;Aug2015, Vol. 64 Issue 8, p137 

    A correction to the article "Pathobiology of Liver Fibrosis †A Translational Success Story" by Y. A. Lee that was published in a 2015 issue of the periodical is presented.

  • Corrections.  // Gut;Aug2015, Vol. 64 Issue 8, p1337 

    A correction to the article "Pathobiology of Liver Fibrosis - A Translational Success Story" by Y. A. Lee that was published in a 2015 issue of the periodical is presented.

  • Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats. Leclercq, I. A.; Sempoux, C.; Stärkel, P.; Horsmans, Y. // Gut;Jul2006, Vol. 55 Issue 7, p1020 

    Aim: Peroxisome proliferator activated receptor γ (PPARγ) agonists have been shown to prevent hepatic fibrosis in rodents. We evaluated the therapeutic antifibrotic potential of the PPARγ agonist pioglitazone on established hepatic fibrosis. Methods: Repeated injections of carbon...

  • Chemokines: potent mediators of hepatic inflammation and fibrosis in chronic liver diseases. Handa, Priya; Kowdley, Kris V. // Annals of Hepatology: Official Journal of the Mexican Associatio;Jan/Feb2014, Vol. 13 Issue 1, p152 

    The article offers information on hepatic inflammation and fibrosis in chronic liver diseases. Chronic liver injury is said to be characterized by inflammation and fibrosis. Hepatocellular carcinoma and end-stage liver disease can be caused by unresolved progression of fibrosis. Chronic...

  • Non-invasive methods for the assessment of hepatic fibrosis: transient elastography, hyaluronic acid, 13C-aminopyrine breath test and cytokeratin 18 fragment. Caviglia, Gian Paolo; Ciancio, Alessia; Rosso, Chiara; Abate, Maria Lorena; Olivero, Antonella; Pellicano, Rinaldo; Touscoz, Giovanni Antonio; Smedile, Antonina; Rizzetto, Mario // Annals of Hepatology: Official Journal of the Mexican Associatio;Jan/Feb2014, Vol. 13 Issue 1, p91 

    Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage. Aim. To investigate...

  • Liver Elastography - An Update. Sporea, Ioan; Gilja, Odd Helge; Bota, Simona; Șirli, Roxana; Popescu, Alina // Medical Ultrasonography;Dec2013, Vol. 15 Issue 4, p304 

    Liver fibrosis evaluation is very important for treatment and prognosis in patients with chronic liver disease. The "goldstandard" method for liver fibrosis assessment is still considered to be the liver biopsy, but in the last years non-invasive methods have increasingly been used, especially...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics