Defining the cellular repertoire of GPCRs identifies a profibrotic role for the most highly expressed receptor, protease-activated receptor 1, in cardiac fibroblasts

FASEB Journal

Volumn 26, Issue 11, 2012, Pages 4540-4547

  Snead, Aaron N ^a   Insel, Paul A ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

7 transmembrane receptors; Cardiac fibrosis; G protein coupled receptors; Myofibroblasts; Thrombin

Indexed keywords

G PROTEIN COUPLED RECEPTOR; MESSENGER RNA; PROTEINASE ACTIVATED RECEPTOR 1; SMALL INTERFERING RNA; THROMBIN;

ANIMAL CELL; ARTICLE; CARDIAC FIBROBLAST; CELL ISOLATION; COLLAGEN SYNTHESIS; CONTROLLED STUDY; FIBROBLAST; GENE SILENCING; HEART FUNCTION; MALE; MYOFIBROBLAST; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; CELLS, CULTURED; FIBROBLASTS; FIBROSIS; GENE EXPRESSION REGULATION; MALE; MYOCARDIUM; OLIGOPEPTIDES; RATS; RECEPTOR, PAR-1; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; THROMBIN;

RATTUS; RATTUS NORVEGICUS;

EID: 84868275428     PISSN: None     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.12-213496     Document Type: Article

References (41)

1. Gabbiani, G. (2003) The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol. 200, 500-503
2. Hunyady, L., and Catt, K. J. (2006) Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol. Endocrinol. 20, 953-970
3. Oro, C., Qian, H., and Thomas, W. G. (2007) Type 1 angiotensin receptor pharmacology: signaling beyond G proteins. Pharmacol. Ther. 113, 210-226
4. Ruster, C., and Wolf, G. (2011) Angiotensin II as a morphogenic cytokine stimulating renal fibrogenesis. J. Am. Soc. Nephrol. 22, 1189-1199
5. Vignon-Zellweger, N., Heiden, S., Miyauchi, T., and Emoto, N. (2012) Endothelin and endothelin receptors in the renal and cardiovascular systems. [E-pub ahead of print] Life Sci. doi: 10.1016/j.lfs.2012.03.026
6. Overington, J. P., Al-Lazikani, B., and Hopkins, A. L. (2006) How many drug targets are there? Nat. Rev. Drug Discov. 5, 993-996
7. Hansen, A., Chen, Y., Inman, J. M., Phan, Q. N., Qi, Z. Q., Xiang, C. C., Palkovits, M., Cherman, N., Kuznetsov, S. A., Robey, P. G., Mezey, E., and Brownstein, M. J. (2007) Sensitive and specific method for detecting G protein-coupled receptor mRNAs. Nat. Methods 4, 35-37
8. Regard, J. B., Sato, I. T., and Coughlin, S. R. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell 135, 561-571
9. Einstein, R., Jordan, H., Zhou, W., Brenner, M., Moses, E. G., and Liggett, S. B. (2008) Alternative splicing of the G proteincoupled receptor superfamily in human airway smooth muscle diversifies the complement of receptors. Proc. Natl. Acad. Sci. U. S. A. 105, 5230-5235
10. Moore-Morris, T., Varrault, A., Mangoni, M. E., Le Digarcher, A., Negre, V., Dantec, C., Journot, L., Nargeot, J., and Couette, B. (2009) Identification of potential pharmacological targets by analysis of the comprehensive G protein-coupled receptor repertoire in the four cardiac chambers. Mol. Pharmacol. 75, 1108-1116
11. Swaney, J. S., Roth, D. M., Olson, E. R., Naugle, J. E., Meszaros, J. G., and Insel, P. A. (2005) Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase. Proc. Natl. Acad. Sci. U. S. A. 102, 437-442
12. Lu, D., Soleymani, S., Madakshire, R., and Insel, P. A. (2012) ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors. FASEB J. 26, 2580-2591
13. Yokoyama, U., Minamisawa, S., Adachi-Akahane, S., Akaike, T., Naguro, I., Funakoshi, K., Iwamoto, M., Nakagome, M., Uemura, N., Hori, H., Yokota, S., and Ishikawa, Y. (2006) Multiple transcripts of Ca2-channel alpha1-subunits and a novel spliced variant of the alpha1C-subunit in rat ductus arteriosus. Am. J. Physiol. Heart Circ. Physiol. 290, H1660-1670
14. Sabri, A., Short, J., Guo, J., and Steinberg, S. F. (2002) Proteaseactivated receptor-1-mediated DNA synthesis in cardiac fibroblast is via epidermal growth factor receptor transactivation: distinct PAR-1 signaling pathways in cardiac fibroblasts and cardiomyocytes. Circ. Res. 91, 532-539
15. Obreztchikova, M., Elouardighi, H., Ho, M., Wilson, B. A., Gertsberg, Z., and Steinberg, S. F. (2006) Distinct signaling functions for Shc isoforms in the heart. J. Biol. Chem. 281, 20197-20204
16. Ozgen, N., Obreztchikova, M., Guo, J., Elouardighi, H., Dorn, G. W., 2nd, Wilson, B. A., and Steinberg, S. F. (2008) Protein kinase D links Gq-coupled receptors to cAMP response elementbinding protein (CREB)-Ser133 phosphorylation in the heart. J. Biol. Chem. 283, 17009-17019
17. Coughlin, S. R. (2005) Protease-Activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost. 3, 1800-1814
18. Steinberg, S. F. (2005) The cardiovascular actions of proteaseactivated receptors. Mol. Pharmacol. 67, 2-11
19. Leger, A. J., Covic, L., and Kuliopulos, A. (2006) Proteaseactivated receptors in cardiovascular diseases. Circulation 114, 1070-1077
20. Coughlin, S. R. (1999) How the protease thrombin talks to cells. Proc. Natl. Acad. Sci. U. S. A. 96, 11023-11027
21. Ghosh, A. K., and Vaughan, D. E. (2012) PAI-1 in tissue fibrosis. J. Cell. Physiol. 227, 493-507
22. Jun, J. I., and Lau, L. F. (2011) Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat. Rev. Drug Discov. 10, 945-963
23. Leask, A. (2010) Potential therapeutic targets for cardiac fibrosis: TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ. Res. 106, 1675-1680
24. Yokoyama, U., Patel, H. H., Lai, N. C., Aroonsakool, N., Roth, D. M., and Insel, P. A. (2008) The cyclic AMP effector Epac integrates pro-And anti-fibrotic signals. Proc. Natl. Acad. Sci. U. S. A. 105, 6386-6391
25. Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., and Brown, R. A. (2002) Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 3, 349-363
26. Dobaczewski, M., Chen, W., and Frangogiannis, N. G. (2011) Transforming growth factor (TGF)-beta signaling in cardiac remodeling. J. Mol. Cell. Cardiol. 51, 600-606
27. Gurtner, G. C., Werner, S., Barrandon, Y., and Longaker, M. T. (2008) Wound repair and regeneration. Nature 453, 314-321
28. Fiorucci, S., Antonelli, E., Distrutti, E., Severino, B., Fiorentina, R., Baldoni, M., Caliendo, G., Santagada, V., Morelli, A., and Cirino, G. (2004) PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology 39, 365-375
29. Zhang, G., Kernan, K. A., Collins, S. J., Cai, X., Lopez-Guisa, J. M., Degen, J. L., Shvil, Y., and Eddy, A. A. (2007) Plasmin(ogen) promotes renal interstitial fibrosis by promoting epithelialto-mesenchymal transition: role of plasmin-Activated signals. J. Am. Soc. Nephrol. 18, 846-859
30. Chambers, R. C. (2008) Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br. J. Pharmacol. 153(Suppl. 1), S367-S378
31. Sullivan, B. P., Weinreb, P. H., Violette, S. M., and Luyendyk, J. P. (2010) The coagulation system contributes to alphaVbeta6 integrin expression and liver fibrosis induced by cholestasis. Am. J. Pathol. 177, 2837-2849
32. Cevikbas, F., Seeliger, S., Fastrich, M., Hinte, H., Metze, D., Kempkes, C., Homey, B., and Steinhoff, M. (2011) Role of protease-Activated receptors in human skin fibrosis and scleroderma. Exp. Dermatol. 20, 69-71
33. Gellings Lowe, N., Swaney, J. S., Moreno, K. M., and Sabbadini, R. A. (2009) Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblasts. Cardiovasc. Res. 82, 303-312
34. Laeremans, H., Rensen, S. S., Ottenheijm, H. C., Smits, J. F., and Blankesteijn, W. M. (2010) Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts. Cardiovasc. Res. 87, 514-523
35. Braun, O. O., Lu, D., Aroonsakool, N., and Insel, P. A. (2010) Uridine triphosphate (UTP) induces profibrotic responses in cardiac fibroblasts by activation of P2Y2 receptors. J. Mol. Cell. Cardiol. 49, 362-369
36. Russo, A., Soh, U. J., and Trejo, J. (2009) Proteases display biased agonism at protease-Activated receptors: location matters. Mol. Interv. 9, 87-96
37. Kishi, K., Nakajima, H., and Tajima, S. (1999) Differential responses of collagen and glycosaminoglycan syntheses and cell proliferation to exogenous transforming growth factor beta 1 in the developing mouse skin fibroblasts in culture. Br. J. Plast. Surg. 52, 579-582
38. Insel, P. A., Murray, F., Yokoyama, U., Romano, S., Yun, H., Brown, L., Snead, A., Lu, D., and Aroonsakool, N. (2012) cAMP and Epac in the regulation of tissue fibrosis. Br. J. Pharmacol. 166, 447-456
39. Strande, J. L., Hsu, A., Su, J., Fu, X., Gross, G. J., and Baker, J. E. (2007) SCH 79797, a selective PAR1 antagonist, limits myocardial ischemia/reperfusion injury in rat hearts. Basic. Res. Cardiol. 102, 350-358
40. Pawlinski, R., Tencati, M., Hampton, C. R., Shishido, T., Bullard, T. A., Casey, L. M., Andrade-Gordon, P., Kotzsch, M., Spring, D., Luther, T., Abe, J., Pohlman, T. H., Verrier, E. D., Blaxall, B. C., and Mackman, N. (2007) Protease-Activated receptor-1 contributes to cardiac remodeling and hypertrophy. Circulation 116, 2298-2306
41. Baker, J. E., Fish, B. L., Su, J., Haworth, S. T., Strande, J. L., Komorowski, R. A., Migrino, R. Q., Doppalapudi, A., Harmann, L., Allen Li, X., Hopewell, J. W., and Moulder, J. E. (2009) 10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model. Int. J. Radiat. Biol. 85, 1089-1100