Divergent signaling pathways cooperatively regulate TGFβ induction of cysteine-rich protein 2 in vascular smooth muscle cells

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• 作者：Meng-Ling Wu (1) (2)
  Chung-Huang Chen (1) (3)
  Yung-Tsang Lin (1)
  Yuan-Jyun Jheng (1)
  Yen-Chun Ho (1) (4)
  Liang-Tung Yang (1)
  Linyi Chen (2)
  Matthew D Layne (5)
  Shaw-Fang Yet (1) (6) (7)
  
• 关键词：Cysteine ; rich protein 2 ; Vascular smooth muscle cells ; TGFβ ; ATF2 ; Smad2/3
• 刊名：Cell Communication and Signaling
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：12
• 期：1
• 全文大小：702 KB
• 参考文献：1. Owens GK, Kumar MS, Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. / Physiol Rev 2004, 84:767-01. CrossRef
  2. Louis HA, Pino JD, Schmeichel KL, Pomies P, Beckerle MC: Comparison of three members of the cysteine-rich protein family reveals functional conservation and divergent patterns of gene expression. / J Biol Chem 1997, 272:27484-7491. CrossRef
  3. Jain MK, Fujita KP, Hsieh CM, Endege WO, Sibinga NE, Yet SF, Kashiki S, Lee WS, Perrella MA, Haber E, Lee ME: Molecular cloning and characterization of SmLIM, a developmentally regulated LIM protein preferentially expressed in aortic smooth muscle cells. / J Biol Chem 1996, 271:10194-0199. CrossRef
  4. Wei J, Gorman TE, Liu X, Ith B, Tseng A, Chen Z, Simon DI, Layne MD, Yet SF: Increased neointima formation in cysteine-rich protein 2-deficient mice in response to vascular injury. / Circ Res 2005, 97:1323-331. CrossRef
  5. Chen CH, Ho YC, Ho HH, Chang IC, Kirsch KH, Chuang YJ, Layne MD, Yet SF: Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration. / Cardiovasc Res 2013, 100:461-71. CrossRef
  6. Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA: Production of transforming growth factor β ₁ during repair of arterial injury. / J Clin Invest 1991, 88:904-10. CrossRef
  7. Yamamoto K, Morishita R, Tomita N, Shimozato T, Nakagami H, Kikuchi A, Aoki M, Higaki J, Kaneda Y, Ogihara T: Ribozyme oligonucleotides against transforming growth factor-β inhibited neointimal formation after vascular injury in rat model: potential application of ribozyme strategy to treat cardiovascular disease. / Circulation 2000, 102:1308-314. CrossRef
  8. Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, Grace AA, Schofield PM, Chauhan A: The serum concentration of active transforming growth factor-β is severely depressed in advanced atherosclerosis. / Nat Med 1995, 1:74-9. CrossRef
  9. Mack CP: Signaling mechanisms that regulate smooth muscle cell differentiation. / Arterioscler Thromb Vasc Biol 2011, 31:1495-505. CrossRef
  10. Guo X, Chen SY: Transforming growth factor-β and smooth muscle differentiation. / World J Biol Chem 2012, 3:41-2. CrossRef
  11. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamate C, Merval R, Fradelizi D, Tedgui A: Inhibition of transforming growth factor-β signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. / Circ Res 2001, 89:930-34. CrossRef
  12. Kobayashi K, Yokote K, Fujimoto M, Yamashita K, Sakamoto A, Kitahara M, Kawamura H, Maezawa Y, Asaumi S, Tokuhisa T, Mori S, Sato Y: Targeted disruption of TGF-β-Smad3 signaling leads to enhanced neointimal hyperplasia with diminished matrix deposition in response to vascular injury. / Circ Res 2005, 96:904-12. CrossRef
  13. Lin DW, Chang IC, Tseng A, Wu ML, Chen CH, Patenaude CA, Layne MD, Yet SF: Transforming growth factor β up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. / J Biol Chem 2008, 283:15003-5014. CrossRef
  14. Derynck R, Feng XH: TGF-β receptor signaling. / Biochim Biophys Acta 1997, 1333:F105-50.
  15. Wygrecka M, Zakrzewicz D, Taborski B, Didiasova M, Kwapiszewska G, Preissner KT, Markart P: TGF-β1 induces tissue factor expression in human lung fibroblasts in a PI3K/JNK/Akt-dependent and AP-1-dependent manner. / Am J Respir Cell Mol Biol 2012, 47:614-27. CrossRef
  16. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landstrom M: The type I TGF-β receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. / Nat Cell Biol 2008, 10:1199-207. CrossRef
  17. Yamashita M, Fatyol K, Jin C, Wang X, Liu Z, Zhang YE: TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-β. / Mol Cell 2008, 31:918-24. CrossRef
  18. Siegel PM, Massague J: Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. / Nat Rev Cancer 2003, 3:807-21. CrossRef
  19. Lopez-Casillas F, Wrana JL, Massague J: Betaglycan presents ligand to the TGFβ signaling receptor. / Cell 1993, 73:1435-444. CrossRef
  20. Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J: Transforming growth factor β signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. / Proc Natl Acad Sci U S A 2003, 100:8430-435. CrossRef
  21. Papadimitriou E, Kardassis D, Moustakas A, Stournaras C: TGFβ-induced early activation of the small GTPase RhoA is Smad2/3-independent and involves Src and the guanine nucleotide exchange factor Vav2. / Cell Physiol Biochem 2011, 28:229-38. CrossRef
  22. Sato M, Kawai-Kowase K, Sato H, Oyama Y, Kanai H, Ohyama Y, Suga T, Maeno T, Aoki Y, Tamura J, Sakamoto H, Nagai R, Kurabayashi M: c-Src and hydrogen peroxide mediate transforming growth factor-β1-induced smooth muscle cell-gene expression in 10?T1/2 cells. / Arterioscler Thromb Vasc Biol 2005, 25:341-47. CrossRef
  23. Chen S, Crawford M, Day RM, Briones VR, Leader JE, Jose PA, Lechleider RJ: RhoA modulates Smad signaling during transforming growth factor-β-induced smooth muscle differentiation. / J Biol Chem 2006, 281:1765-770. CrossRef
  24. Deaton RA, Su C, Valencia TG, Grant SR: Transforming growth factor-β1-induced expression of smooth muscle marker genes involves activation of PKN and p38 MAPK. / J Biol Chem 2005, 280:31172-1181. CrossRef
  25. Zhang YE: Non-Smad pathways in TGF-β signaling. / Cell Res 2009, 19:128-39. CrossRef
  26. Zawel L, Dai JL, Buckhaults P, Zhou S, Kinzler KW, Vogelstein B, Kern SE: Human Smad3 and Smad4 are sequence-specific transcription activators. / Mol Cell 1998, 1:611-17. CrossRef
  27. Bandyopadhyay B, Han A, Dai J, Fan J, Li Y, Chen M, Woodley DT, Li W: TβRI/Alk5-independent TβRII signaling to ERK1/2 in human skin cells according to distinct levels of TβRII expression. / J Cell Sci 2011, 124:19-4. CrossRef
  28. Moustakas A, Heldin CH: Non-Smad TGF-β signals. / J Cell Sci 2005, 118:3573-584. CrossRef
  29. Engel ME, McDonnell MA, Law BK, Moses HL: Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription. / J Biol Chem 1999, 274:37413-7420. CrossRef
  30. Dziembowska M, Danilkiewicz M, Wesolowska A, Zupanska A, Chouaib S, Kaminska B: Cross-talk between Smad and p38 MAPK signalling in transforming growth factor β signal transduction in human glioblastoma cells. / Biochem Biophys Res Commun 2007, 354:1101-106. CrossRef
  31. Liu G, Ding W, Neiman J, Mulder KM: Requirement of Smad3 and CREB-1 in mediating transforming growth factor-β (TGFβ) induction of TGFβ3 secretion. / J Biol Chem 2006, 281:29479-9490. CrossRef
  32. Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, Ishii S: ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-β signaling. / J Biol Chem 1999, 274:8949-957. CrossRef
  33. Hautmann MB, Madsen CS, Owens GK: A transforming growth factor β (TGFβ) control element drives TGFβ-induced stimulation of smooth muscle α-actin gene expression in concert with two CArG elements. / J Biol Chem 1997, 272:10948-0956. CrossRef
  34. Adam PJ, Regan CP, Hautmann MB, Owens GK: Positive- and negative-acting Krüppel-like transcription factors bind a transforming growth factor β control element required for expression of the smooth muscle cell differentiation marker SM22α in vivo. / J Biol Chem 2000, 275:37798-7806. CrossRef
  35. Chang YF, Wei J, Liu X, Chen YH, Layne MD, Yet SF: Identification of a CArG-independent region of the cysteine-rich protein 2 promoter that directs expression in the developing vasculature. / Am J Physiol Heart Circ Physiol 2003, 285:H1675-683.
  36. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA Jr, Wrana JL, Falb D: The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. / Cell 1997, 89:1165-173. CrossRef
  37. Steinmuller L, Thiel G: Regulation of gene transcription by a constitutively active mutant of activating transcription factor 2 (ATF2). / Biol Chem 2003, 384:667-72. CrossRef
  38. Gunther S, Alexander RW, Atkinson WJ, Gimbrone MA Jr: Functional angiotensin II receptors in cultured vascular smooth muscle cells. / J Cell Biol 1982, 92:289-98. CrossRef
  
• 作者单位：Meng-Ling Wu (1) (2)
  Chung-Huang Chen (1) (3)
  Yung-Tsang Lin (1)
  Yuan-Jyun Jheng (1)
  Yen-Chun Ho (1) (4)
  Liang-Tung Yang (1)
  Linyi Chen (2)
  Matthew D Layne (5)
  Shaw-Fang Yet (1) (6) (7)
  
  1. Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan
  2. Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan
  3. Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan
  4. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
  5. Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, USA
  6. Metabolomic Research Center, China Medical University Hospital, Taichung, Taiwan
  7. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
  
• ISSN：1478-811X

文摘

Background Vascular smooth muscle cells (VSMCs) of the arterial wall play a critical role in the development of occlusive vascular diseases. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed LIM-only protein, which functionally limits VSMC migration and protects against pathological vascular remodeling. The multifunctional cytokine TGFβ has been implicated to play a role in the pathogenesis of atherosclerosis through numerous downstream signaling pathways. We showed previously that TGFβ upregulates CRP2 expression; however, the detailed signaling mechanisms remain unclear. Results TGFβ treatment of VSMCs activated both Smad2/3 and ATF2 phosphorylation. Individually knocking down Smad2/3 or ATF2 pathways with siRNA impaired the TGFβ induction of CRP2, indicating that both contribute to CRP2 expression. Inhibiting TβRI kinase activity by SB431542 or TβRI knockdown abolished Smad2/3 phosphorylation but did not alter ATF2 phosphorylation, indicating while Smad2/3 phosphorylation was TβRI-dependent ATF2 phosphorylation was independent of TβRI. Inhibiting Src kinase activity by SU6656 suppressed TGFβ-induced RhoA and ATF2 activation but not Smad2 phosphorylation. Blocking ROCK activity, the major downstream target of RhoA, abolished ATF2 phosphorylation and CRP2 induction but not Smad2 phosphorylation. Furthermore, JNK inhibition with SP600125 reduced TGFβ-induced ATF2 (but not Smad2) phosphorylation and CRP2 protein expression while ROCK inhibition blocked JNK activation. These results indicate that downstream of TβRII, Src family kinase-RhoA-ROCK-JNK signaling pathway mediates TβRI-independent ATF2 activation. Promoter analysis revealed that the TGFβ induction of CRP2 was mediated through the CRE and SBE promoter elements that were located in close proximity. Conclusions Our results demonstrate that two signaling pathways downstream of TGFβ converge on the CRE and SBE sites of the Csrp2 promoter to cooperatively control CRP2 induction in VSMCs, which represents a previously unrecognized mechanism of VSMC gene induction by TGFβ.