Identification of RARRES1 as a core regulator in liver fibrosis
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- 作者：Andreas Teufel (1)
Diana Becker (1)
Susanne N. Weber (2)
Steven Dooley (3)
Katja Breitkopf-Heinlein (3)
Thorsten Maass (1)
Katrin Hochrath (2)
Markus Krupp (1)
Jens U. Marquardt (1)
Martin Kolb (4)
Bernhard Korn (5)
Christof Niehrs (5) (6)
Tim Zimmermann (1)
Patricio Godoy (7)
Peter R. Galle (1)
Frank Lammert (2) - 关键词：Bioinformatics ; Comparative genomics ; Hepatic fibrosis ; Genetics ; Transcriptome
- 刊名：Journal of Molecular Medicine
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：90
- 期：12
- 页码：1439-1447
- 全文大小：444KB
- 参考文献：1. Friedman SL (2003) Liver fibrosis—from bench to bedside. J Hepatol 38(Suppl 1):S38–S53 CrossRef
2. Gines P, Cardenas A, Arroyo V, Rodes J (2004) Management of cirrhosis and ascites. N Engl J Med 350:1646-654 CrossRef
3. Weber S, Gressner OA, Hall R, Grunhage F, Lammert F (2008) Genetic determinants in hepatic fibrosis: from experimental models to fibrogenic gene signatures in humans. Clin Liver Dis 12:747-57 CrossRef
4. Mehal WZ, Iredale J, Friedman SL (2011) Scraping fibrosis: expressway to the core of fibrosis. Nat Med 17:552-53 CrossRef
5. Sayers EW, Barrett T, Benson DA, Bolton E, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Federhen S et al (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 39:D38–D51 CrossRef
6. Sherlock G, Hernandez-Boussard T, Kasarskis A, Binkley G, Matese JC, Dwight SS, Kaloper M, Weng S, Jin H, Ball CA et al (2001) The Stanford Microarray Database. Nucleic Acids Res 29:152-55 CrossRef
7. http://www.r-project.org
8. http://www.bioconductor.org
9. http://www.perl.org
10. http://www.ingenuity.com
11. http://www.genego.com
12. Farkas L, Farkas D, Ask K, Moller A, Gauldie J, Margetts P, Inman M, Kolb M (2009) VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 119:1298-311 CrossRef
13. Jamall IS, Davis B (1991) Chemicals and environmentally caused diseases in developing countries. Infect Dis Clin North Am 5:365-75
14. Breitkopf K, Roeyen C, Sawitza I, Wickert L, Floege J, Gressner AM (2005) Expression patterns of PDGF-A, -B, -C and -D and the PDGF-receptors alpha and beta in activated rat hepatic stellate cells (HSC). Cytokine 31:349-57 CrossRef
15. Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA (1996) Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin. J Investig Dermatol 106:269-74 CrossRef
16. Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann CW (1998) Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium. J Cell Sci 111(Pt 14):2043-054
17. Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T (1994) Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:408-19 CrossRef
18. Okuno M, Kojima S, Akita K, Matsushima-Nishiwaki R, Adachi S, Sano T, Takano Y, Takai K, Obora A, Yasuda I et al (2002) Retinoids in liver fibrosis and cancer. Front Biosci 7:d204–d218 CrossRef
19. Castle JC, Armour CD, Lower M, Haynor D, Biery M, Bouzek H, Chen R, Jackson S, Johnson JM, Rohl CA et al (2010) Digital genome-wide ncRNA expression, including SnoRNAs, across 11 human tissues using polyA-neutral amplification. PLoS One 5:e11779 CrossRef
20. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, Yee H, Zender L, Lowe SW (2008) Senescence of activated stellate cells limits liver fibrosis. Cell 134:657-67 CrossRef
21. Parkinson H, Sarkans U, Kolesnikov N, Abeygunawardena N, Burdett T, Dylag M, Emam I, Farne A, Hastings E, Holloway E et al (2011) ArrayExpress update—an archive of microarray and high-throughput sequencing-based functional genomics experiments. Nucleic Acids Res 39:D1002–D1004 CrossRef
22. Saddic LA, Wirt S, Vogel H, Felsher DW, Sage J (2011) Functional interactions between retinoblastoma and c-MYC in a mouse model of hepatocellular carcinoma. PLoS One 6:e19758 CrossRef
23. Constandinou C, Henderson N, Iredale JP (2005) Modeling liver fibrosis in rodents. Methods Mol Med 117:237-50
24. Rodt T, von Falck C, Dettmer S, Halter R, Maus R, Ask K, Kolb M, Gauldie J, Langer F, Hoy L et al (2010) Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-beta1. Respir Res 11:181 CrossRef
25. Schirmacher P, Fleig WE, Dienes HP (2004) Biopsy diagnosis of chronic hepatitis. Z Gastroenterol 42:175-85 CrossRef
26. Czochra P, Klopcic B, Meyer E, Herkel J, Garcia-Lazaro JF, Thieringer F, Schirmacher P, Biesterfeld S, Galle PR, Lohse AW et al (2006) Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. J Hepatol 45:419-28 CrossRef
27. Parsons CJ, Takashima M, Rippe RA (2007) Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol 22(Suppl 1):S79–S84 CrossRef
28. Bonner JC (2004) Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 15(4):255-73 CrossRef
29. Sahab ZJ, Hall MD, Zhang L, Cheema AK, Byers SW (2010) Tumor suppressor RARRES1 regulates DLG2, PP2A, VCP, EB1, and Ankrd26. J Cancer 1:14-2 CrossRef
30. Bonazzi VF, Irwin D, Hayward NK (2009) Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma. Gene Chromosome Cancer 48:10-1 CrossRef
31. Yanatatsaneejit P, Chalermchai T, Kerekhanjanarong V, Shotelersuk K, Supiyaphun P, Mutirangura A, Sriuranpong V (2008) Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma. Oral Oncol 44:400-06 CrossRef
32. Wu CC, Shyu RY, Chou JM, Jao SW, Chao PC, Kang JC, Wu ST, Huang SL, Jiang SY (2006) RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma. Eur J Cancer 42:557-65 CrossRef - 作者单位：Andreas Teufel (1)
Diana Becker (1)
Susanne N. Weber (2)
Steven Dooley (3)
Katja Breitkopf-Heinlein (3)
Thorsten Maass (1)
Katrin Hochrath (2)
Markus Krupp (1)
Jens U. Marquardt (1)
Martin Kolb (4)
Bernhard Korn (5)
Christof Niehrs (5) (6)
Tim Zimmermann (1)
Patricio Godoy (7)
Peter R. Galle (1)
Frank Lammert (2)
1. Department of Medicine I, Johannes Gutenberg University, Building 605, Langenbeckstr. 1, 55101, Mainz, Germany
2. Department of Medicine II, Saarland University Medical Center, Homburg, Germany
3. Molecular Hepatology—Alcohol Associated Diseases, II. Medical Clinic, Medical Faculty Mannheim at Heidelberg University, Heidelberg, Germany
4. Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada
5. Institute of Molecular Biology, Mainz, Germany
6. Division of Molecular Embryology, German Cancer Research Center, DKFZ, Heidelberg, Germany
7. Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany - ISSN：1432-1440
文摘
Genetic factors contribute to progression and modulation of hepatic fibrosis. High throughput genomics/transcriptomics approaches aiming at identifying key regulators of fibrosis development are tainted with the difficulty of separating essential biological “driver-from modifier genes. We applied a comparative transcriptomics approach and investigated fibrosis development in different organs to identify overlapping expression changes, since these genes may be part of core pathways in fibrosis development. Gene expression was analysed on publicly available microarray data from liver, lung and kidney fibrosis. RARRES1, AGER and S100A2 were differentially regulated in all fibrosis experiments. RARRES1 was extensively analysed by means of advanced bioinformatics analyses and functional studies. Microarray and Western Blot analysis of a standard liver fibrosis model (CCl4) demonstrated an early induction of RARRES1 mRNA and protein expression. In addition, quantitative RT-PCR in tissue samples from patients with advanced liver fibrosis showed higher expression as compared to non-fibrotic biopsies. Microarray analysis of RARRES1 overexpressing cells identified an enrichment of a major signature associated with fibrosis. Furthermore, RARRES1 expression increased during in vitro activation of hepatic stellate cells. To further verify the pro-fibrogenic role across organs, we demonstrated an increase in RARRES1 expression in a rat lung fibrosis model induced by adenoviral TGF-β1 induction. We have performed a comparative transcriptomics analysis in order to identify core pathways of liver fibrogenesis, confirmed a candidate gene and enlightened the up- and downstream mechanisms of its action leading to fibrosis across organs and species.