nach oben

Erschienen in:

01.03.2010 | Original Contribution

FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK

verfasst von: Emmanuel Chorianopoulos, Thomas Heger, Matthias Lutz, Derk Frank, Florian Bea, Hugo A. Katus, Norbert Frey

Erschienen in: Basic Research in Cardiology | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Proinflammatory cytokines, including TNF family members, have been shown to play a critical role in cardiac remodeling. FGF-inducible 14-kDa protein (Fn14, TNFrsf12a or TWEAKR) is the smallest member of the TNF-receptor family. Currently, little is known about the functional role of Fn14 and its only known ligand TNF-like weak inducer of apoptosis (TWEAK) in the heart. We therefore evaluated the expression and regulation of Fn14 in cardiomyocytes and in experimental myocardial infarction. In order to study the regulation of Fn14, myocardial infarction was induced in CD-1 mice and neonatal rat cardiomyocytes were used for in vitro studies. TWEAK and Fn14 were markedly upregulated in the remodeling myocardium after experimental myocardial infarction in vivo. Likewise, fibroblast growth factor 1, norepinephrine and angiotensin II as well as mechanical stretch were able to strongly induce Fn14 expression in cardiomyocytes. This induction is mediated via the Rho/ROCK pathway, since the known inhibitors C3 exoenzyme for RhoA and Y27632 for ROCK prevented the upregulation of Fn14 in cardiomyocytes. Consistently, pretreatment of cardiomyocytes with siRNA against Rho A and ROCK also abolished Fn14 induction. Moreover, stimulation of cardiomyocytes with TWEAK promoted nuclear translocation of NF-κB and subsequent induction of NF-κB dependent genes such as RANTES and MCP-1. Conversely, when cells were pretreated with siRNA against Fn14, NF-κB activation by TWEAK was inhibited. We here provide the first evidence of a stress-induced regulation of the TWEAK/Fn14 axis in cardiomyocytes implying a role of the TWEAK/Fn14 pathway in cardiac remodeling.

Nur mit Berechtigung zugänglich

Aikawa R, Komuro I, Nagai R, Yazaki Y (2000) Rho plays an important role in angiotensin II-induced hypertrophic responses in cardiac myocytes. Mol Cell Biochem 212:177–182CrossRefPubMed

Anker SD, Coats AJ (2002) How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 86:123–130CrossRefPubMed

Aukrust P, Ueland T, Müller F, Andreassen AK, Nordøy I, Aas H, Kjekshus J, Simonsen S, Frøland SS, Gullestad L (1998) Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation 97:1136–1143PubMed

Behr TM, Wang X, Aiyar N, Coatney RW, Li X, Koster P, Angermann CE, Ohlstein E, Feuerstein GZ, Winaver J (2000) Monocyte chemoattractant protein-1 is upregulated in rats with volume-overload congestive heart failure. Circulation 102:1315–1322PubMed

Bover LC, Cardó-Vila M, Kuniyasu A, Sun J, Rangel R, Takeya M, Aggarwal BB, Arap W, Pasqualini R (2007) A previously unrecognized protein–protein interaction between TWEAK and CD163: potential biological implications. J Immunol 178:8183–8194PubMed

Brown SAN, Richards CM, Hanscom HN, Feng SL, Winkles JA (2003) The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kB activation. Biochem J 371:395–403CrossRefPubMed

Campbell S, Burkly LC, Gao HX, Berman JW, Su L, Browning B, Zheng T, Schiffer L, Michaelson JS, Putterman C (2006) Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells. J Immunol 176:1889–1898PubMed

Celis R, Torre-Martinez G, Torre-Amione G (2008) Evidence for activation of immune system in heart failure: is there a role for anti-inflammatory therapy? Curr Opin Cardiol 23:254–260CrossRefPubMed

Chen D, Assad-Kottner C, Orrego C, Torre-Amione G (2008) Cytokines and acute heart failure. Crit Care Med 36:S9–S16CrossRefPubMed

10.

Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT (2003) Randomized, double-blind, placebo controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation 107:3133–3140CrossRefPubMed

11.

Cuenca J, Goren N, Prieto P, Martín-Sanz P, Boscá L (2007) Selective impairment of nuclear factor-kappaB-dependent gene transcription in adult cardiomyocytes: relevance for the regulation of the inflammatory response in the heart. Am J Pathol 171:820–828CrossRefPubMed

12.

Damås JK, Eiken HG, Oie E, Bjerkeli V, Yndestad A, Ueland T, Tonnessen T, Geiran OR, Aass H, Simonsen S, Christensen G, Froland SS, Attramadal H, Gullestad L, Aukrust P (2000) Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure. Cardiovasc Res 47:778–787CrossRefPubMed

13.

Deswal A, Bozkurt B, Seta Y, Parilti-Eiswirth S, Hayes FA, Blosch C, Mann DL (1999) Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation 99:3224–3226PubMed

14.

Dogra C, Changotra H, Mohan S, Kumar A (2006) Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-kappaB and degradation of MyoD protein. J Biol Chem 281:10327–10336CrossRefPubMed

15.

Dogra C, Changotra H, Wedhas N, Qin X, Wergedal JE, Kumar A (2007) TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J 21:1857–1869CrossRefPubMed

16.

Dogra C, Hall SL, Wedhas N, Linkhart TA, Kumar A (2007) Fibroblast growth factor inducible 14 (Fn14) is required for the expression of myogenic regulatory factors and differentiation of myoblasts into myotubes. Evidence for TWEAK-independent functions of Fn14 during myogenesis. J Biol Chem 282:15000–15010CrossRefPubMed

17.

Feng SL, Guo Y, Factor VM, Thorgeirsson SS, Bell DW, Testa JR, Peifley KA, Winkles JA (2000) The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. Am J Pathol 156:1253–1261PubMed

18.

Ferrari R, Bachetti T, Confortini R, Opasich C, Febo O, Corti A, Cassani G, Visioli O (1995) Tumour necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation 92:1479–1486PubMed

19.

Frank D, Kuhn C, Brors B, Hanselmann C, Lüdde M, Katus HA, Frey N (2008) Gene expression pattern in biomechanically stretched cardiomyocytes: evidence for a stretch-specific gene program. Hypertension 51:309–318CrossRefPubMed

20.

Frantz S, Hu K, Adamek A, Wolf J, Sallam A, Maier SK, Lonning S, Ling H, Ertl G, Bauersachs J (2008) Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res Cardiol 103:485–492CrossRefPubMed

21.

Gallagher G, Menzie S, Huang Y, Jackson C, Hunyor SN (2007) Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep. Basic Res Cardiol 102:63–72CrossRefPubMed

22.

Grabellus F, Levkau B, Sokoll A, Welp H, Schmid C, Deng MC, Takeda A, Breithardt G, Baba HA (2002) Reversible activation of nuclear factor kappa B in human end-stage heart failure after left ventricular mechanical support. Cardiovasc Res 53:124–130CrossRefPubMed

23.

Hamid T, Gu Y, Ortines RV, Bhattacharya C, Wang G, Xuan YT, Prabhu SD (2009) Divergent tumor necrosis factor receptor-related remodeling responses in heart failure: role of nuclear factor-kappaB and inflammatory activation. Circulation 119:1386–1397CrossRefPubMed

24.

Han S, Yoon K, Lee K, Kim K, Jang H, Lee NK, Hwang K, Young Lee S (2003) TNF related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-kappa B through TNF receptor-associated factors. Biochem Biophys Res Commun 305:789–796CrossRefPubMed

25.

Hayashidani S, Tsutsui H, Shiomi T, Ikeuchi M, Matsusaka H, Suematsu N, Wen J, Egashira K, Takeshita A (2003) Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 108:2134–2140CrossRefPubMed

26.

Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, Dyspersin GD, Cleutjens JP, Shipley M, Angellilo A, Levi M, Nübe O, Baker A, Keshet E, Lupu F, Herbert JM, Smits JF, Shapiro SD, Baes M, Borgers M, Collen D, Daemen MJ, Carmeliet P (1999) Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 5:1135–1142CrossRefPubMed

27.

Heymans S, Lupu F, Terclavers S, Vanwetswinkel B, Herbert JM, Baker A, Collen D, Carmeliet P, Moons L (2005) Loss or inhibition of uPA or MMP-9 attenuates LV remodeling and dysfunction after acute pressure overload in mice. Am J Pathol 166:15–25PubMed

28.

Hirotani S, Otsu K, Nishida K, Higuchi Y, Morita T, Nakayama H, Yamaguchi O, Mano T, Matsumura Y, Ueno H, Tada M, Hori M (2002) Involvement of nuclear factor-kappaB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy. Circulation 105:509–515CrossRefPubMed

29.

Jain M, Jakubowski A, Cui L, Shi J, Su L, Bauer M, Guan J, Lim CC, Naito Y, Thompson JS, Sam F, Ambrose C, Parr M, Crowell T, Lincecum JM, Wang MZ, Hsu YM, Zheng TS, Michaelson JS, Liao R, Burkly LC (2009) A novel role for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the development of cardiac dysfunction and failure. Circulation 119:2058–2068CrossRefPubMed

30.

Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323:236–241PubMed

31.

Lynch CN, Wang YC, Lund JK, Chen Y, Leal JA, Wiley SR (1999) TWEAK induces angiogenesis and proliferation of endothelial cells. J Biol Chem 274:8455–8459CrossRefPubMed

32.

Meighan-Mantha RL, Hsu DK, Guo Y, Brown SA, Feng SL, Peifley KA, Alberts GF, Copeland NG, Gilbert DJ, Jenkins NA, Richards CM, Winkles JA (1999) The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration. J Biol Chem 274:33166–33176CrossRefPubMed

33.

Muñoz-García B, Martín-Ventura JL, Martínez E, Sánchez S, Hernández G, Ortega L, Ortiz A, Egido J, Blanco-Colio LM (2006) Fn14 is upregulated in cytokine-stimulated vascular smooth muscle cells and is expressed in human carotid atherosclerotic plaques: modulation by atorvastatin. Stroke 37:2044–2053CrossRefPubMed

34.

Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA (2006) Controversies in ventricular remodelling. Lancet 367:356–367CrossRefPubMed

35.

Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E (1979) Myocardial infarct size and ventricular function in rats. Circ Res 44:503–512PubMed

36.

Polavarapu R, Gongora MC, Winkles JA, Yepes M (2005) Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-κB pathway activation. J Neurosci 25:10094–10100CrossRefPubMed

37.

Purcell NH, Tang G, Yu C, Mercurio F, DiDonato JA, Lin A (2001) Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc Natl Acad Sci USA 98:6668–6673CrossRefPubMed

38.

Sah VP, Hoshijima M, Chien KR, Brown JH (1996) Rho is required for Galphaq and alpha1-adrenergic receptor signaling in cardiomyocytes. Dissociation of Ras and Rho pathways. J Biol Chem 271:31185–31190CrossRefPubMed

39.

Satoh M, Minami Y, Takahashi Y, Nakamura M (2008) Immune modulation: role of the inflammatory cytokine cascade in the failing human heart. Curr Heart Fail Rep 5:69–74CrossRefPubMed

40.

Schulz R, Heusch G (2009) Tumor necrosis factor-alpha and its receptors 1 and 2: Yin and Yang in myocardial infarction? Circulation 119:1355–1357CrossRefPubMed

41.

Seta Y, Shan K, Bozkurt B, Oral H, Mann DL (1996) Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail 2:243–249CrossRefPubMed

42.

Shioi T, Matsumori A, Kihara Y, Inoko M, Ono K, Iwanaga Y, Yamada T, Iwasaki A, Matsushima K, Sasayama S (1997) Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload. Circ Res 81:664–671PubMed

43.

Skyschally A, Gres P, Hoffmann S, Haude M, Erbel R, Schulz R, Heusch G (2007) Bidirectional role of tumor necrosis factor-alpha in coronary microembolization: progressive contractile dysfunction versus delayed protection against infarction. Circ Res 100:140–146CrossRefPubMed

44.

Tanabe K, Bonilla I, Winkles JA, Strittmatter SM (2003) Fibroblast growth factor-inducible-14 is induced in axotomized neurons and promotes neurite outgrowth. J Neurosci 23:9675–9686PubMed

45.

Tran NL, McDonough WS, Savitch BA, Fortin SP, Winkles JA, Symons M, Nakada M, Cunliffe HE, Hostetter G, Hoelzinger DB, Rennert JL, Michaelson JS, Burkly LC, Lipinski CA, Loftus JC, Mariani L, Berens ME (2006) Increased fibroblast growth factor inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kB and correlate with poor patient outcome. Cancer Res 66:9535–9542CrossRefPubMed

46.

Tran NL, McDonough WS, Savitch BA, Sawyer TF, Winkles JA, Beren ME (2005) The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) fibroblast growth factor-inducible 14 (Fn14) signaling system regulates glioma cell via NFkappaB pathway activation and BCL-XL/BCL-W expression. J Chem 280:3483–3492

47.

Torre-Amione G (2005) Immune activation in chronic heart failure. Am J Cardiol 95:3C–8CCrossRefPubMed

48.

Vince JE, Chau D, Callus B, Wong WW, Hawkins CJ, Schneider P, McKinlay M, Benetatos CA, Condon SM, Chunduru SK, Yeoh G, Brink R, Vaux DL, Silke J (2008) TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha. J Cell Biol 182:171–184CrossRefPubMed

49.

Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, Liu H, Daniel TO, Smith CA, Fanslow WC (2001) A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity 15:837–846CrossRefPubMed

50.

Winkles JA (2008) The TWEAK–Fn14 cytokine–receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov 7:411–425CrossRefPubMed

51.

Yamakawa T, Tanaka S, Numaguchi K, Yamakawa Y, Motley ED, Ichihara S, Inagami T (2000) Involvement of Rho-kinase in angiotensin II-induced hypertrophy of rat vascular smooth muscle cells. Hypertension 35:313–318PubMed

52.

Yang M, Wu J, Martin CM, Kvietys PR, Rui T (2008) Important role of p38 MAP kinase/NF-kappaB signaling pathway in the sepsis-induced conversion of cardiac myocytes to a proinflammatory phenotype. Am J Physiol Heart Circ Physiol 294:H994–H1001CrossRefPubMed

53.

Yepes M, Brown SAN, Moore EG, Smith EP, Lawrence DA, Winkles JA (2005) A soluble Fn14-Fc decoy receptor reduces infarct volume in a murine model of cerebral ischemia. Am J Pathol 166:511–520PubMed

54.

Zhou L, Azfer A, Niu J, Graham S, Choudhury M, Adamski FM, Younce C, Binkley PF, Kolattukudy PE (2006) Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ Res 98:1177–1185CrossRefPubMed

Titel: FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK
verfasst von: Emmanuel Chorianopoulos
Thomas Heger
Matthias Lutz
Derk Frank
Florian Bea
Hugo A. Katus
Norbert Frey
Publikationsdatum: 01.03.2010
Verlag: D. Steinkopff-Verlag
Erschienen in: Basic Research in Cardiology / Ausgabe 2/2010
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-009-0046-y

Neu im Fachgebiet Kardiologie

25.04.2024 | Hypertonie | Nachrichten

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK

Abstract

Neu im Fachgebiet Kardiologie

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Myokarditis nach Infekt – Richtig schwierig wird es bei Profisportlern

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Update Kardiologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2010

Transcriptional regulation of Pim-1 kinase in vascular smooth muscle cells and its role for proliferation

K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum

Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium

Inhibition of mitochondrial permeability transition pore opening: the holy grail of cardioprotection

Simvastatin in contrast to postconditioning reduces infarct size in hyperlipidemic rabbits: possible role of oxidative/nitrosative stress attenuation

Protein kinase C α and ε phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium

Neu im Fachgebiet Kardiologie

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Myokarditis nach Infekt – Richtig schwierig wird es bei Profisportlern

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Update Kardiologie