Hypoxia induces downregulation of PPAR-γ in isolated pulmonary arterial smooth muscle cells and in rat lung via transforming growth factor-β signaling

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volumn 301, Issue 6, 2011, Pages

  Gong, Kaizheng ^a,c   Xing, Dongqi ^a   Li, Peng ^a   Aksut, Baran ^a   Ambalavanan, Namasivayam ^b   Yang, Qinglin ^b   Nozell, Susan E ^b   Oparil, Suzanne ^a   Chen, Yiu Fai ^a  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c YANGZHOU UNIVERSITY   (China)

Author keywords

Peroxisome proliferator activated receptor ; Pulmonary vascular remodeling

Indexed keywords

4 [4 (1,3 BENZODIOXOL 5 YL) 5 (2 PYRIDINYL) 1H IMIDAZOL 2 YL]BENZAMIDE; GROWTH FACTOR; HISTONE DEACETYLASE 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; ROSIGLITAZONE; SMAD PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; HYPOXIA; LUNG; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PULMONARY ARTERY; RAT; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER;

ANIMALS; ANOXIA; CELL HYPOXIA; CELL MOVEMENT; CELLS, CULTURED; DOWN-REGULATION; EXTRACELLULAR MATRIX; HISTONE DEACETYLASE 1; LUNG; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; PPAR GAMMA; PROTEIN-SERINE-THREONINE KINASES; PULMONARY ARTERY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSCRIPTION, GENETIC; TRANSFORMING GROWTH FACTOR BETA;

EID: 82855176909     PISSN: 10400605     EISSN: 15221504     Source Type: Journal    
DOI: 10.1152/ajplung.00062.2011     Document Type: Article

References (33)

1. Ambalavanan N, Nicola T, Hagood J, Bulger A, Serra R, Murphy-Ullrich J, Oparil S, Chen YF. Transforming growth factor-β signaling mediates hypoxia-induced pulmonary arterial remodeling and inhibition of alveolar development in newborn mouse lung. Am J Physiol Lung Cell Mol Physiol 295: L86-L95, 2008.
2. Ameshima S, Golpon H, Cool CD, Chan D, Vandivier RW, Gardai SJ, Wick M, Nemenoff RA, Geraci MW, Voelkel NF. Peroxisome proliferator- activated receptor gamma (PPAR gamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth. Circ Res 92: 1162-1169, 2003.
3. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 121: 2045-2066, 2010.
4. Bobik A. Transforming growth factor-betas and vascular disorders. Arterioscler Thromb Vasc Biol 26: 1712-1720, 2006.
5. Chen YF, Feng JA, Li P, Xing D, Zhang Y, Serra R, Ambalavanan N, Majid-Hassan E, Oparil S. Dominant negative mutation of the TGF-β receptor blocks hypoxia-induced pulmonary vascular remodeling. J Appl Physiol 100: 564-571, 2006.
6. Crossno JT Jr, Garat CV, Reusch JEB, Morris KG, Dempsey EC, McMurtry IF, Stenmark KR, Klemm DJ. Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling. Am J Physiol Lung Cell Mol Physiol 292: L885-L897, 2007.
7. Fu M, Zhang J, Lin Y, Zhu X, Zhao L, Ahmad M, Ehrengruber MU, Chen YE. Early stimulation and late inhibition of peroxisome proliferatoractivated receptor gamma (PPAR gamma) gene expression by transforming growth factor beta in human aortic smooth muscle cells: role of early growth-response factor-1 (Egr-1), activator protein 1 (AP1) and Smads. Biochem J 370: 1019-1025, 2003.
8. Gough NR. Kinase-independent signaling from TGF-beta receptors to TAK1. Sci Signal 1: ec348, 2008.
9. Guignabert C, Alvira CM, Alastalo TP, Sawada H, Hansmann G, Zhao M, Wang L, El-Bizri N, Rabinovitch M. Tie2-mediated loss of peroxisome proliferator-activated receptor-γ in mice causes PDGF receptor- γ-dependent pulmonary arterial muscularization. Am J Physiol Lung Cell Mol Physiol 297: L1082-L1090, 2009.
10. Hamblin M, Chang L, Fan Y, Zhang J, Chen YE. PPARs and the cardiovascular system. Antioxid Redox Signal 11: 1415-1452, 2009.
11. Hansmann G, de Jesus Perez VA, Alastalo TP, Alvira CM, Guignabert C, Bekker JM, Schellong S, Urashima T, Wang L, Morrell NW, Rabinovitch M. An antiproliferative BMP-2/PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension. J Clin Invest 118: 1846-1857, 2008.
12. Hansmann G, Wagner RA, Schellong S, de Jesus Perez VA, Urashima T, Wang L, Sheikh AY, Suen RS, Stewart DJ, Rabinovitch M. Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. Circulation 115: 1275-1284, 2007.
13. Hansmann G, Zamanian RT. PPARgamma activation: a potential treatment for pulmonary hypertension. Sci Transl Med 1: 12ps14, 2009.
14. Jeffery TK, Morrell NW. Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis 45: 173-202, 2002.
15. Kim EK, Lee JH, Oh YM, Lee YS, Lee SD. Rosiglitazone attenuates hypoxia-induced pulmonary arterial hypertension in rats. Respirology 15: 659-668, 2010.
16. Lee G, Elwood F, McNally J, Weiszmann J, Lindstrom M, Amaral K, Nakamura M, Miao S, Cao P, Learned RM, Chen JL, Li Y. T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities. J Biol Chem 277: 19649-19657, 2002.
17. Li P, Oparil S, Feng W, Chen YF. Hypoxia-responsive growth factors upregulate periostin and osteopontin expression via distinct signaling pathways in rat pulmonary arterial smooth muscle cells. J Appl Physiol 97: 1550-1558, 2004.
18. Li P, Oparil S, Novak L, Cao X, Shi W, Lucas J, Chen YF. ANP signaling inhibits TGF-β-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells. J Appl Physiol 102: 390-398, 2007.
19. Li P, Wang D, Lucas J, Oparil S, Xing D, Cao X, Novak L, Renfrow MB, Chen YF. Atrial natriuretic peptide inhibits transforming growth factor-beta-induced smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circ Res 102: 185-192, 2008.
20. Long L, Crosby A, Yang X, Southwood M, Upton PD, Kim DK, Morrell NW. Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension: potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease. Circulation 119: 566-576, 2009.
21. Lucas JA, Zhang Y, Li P, Gong K, Miller AP, Hassan E, Hage F, Xing D, Wells B, Oparil S, Chen YF. Inhibition of transforming growth factor-β signaling induces left ventricular dilation and dysfunction in the pressure-overloaded heart. Am J Physiol Heart Circ Physiol 298: H424- H432, 2010.
22. Milam JE, Keshamouni VG, Phan SH, Hu B, Gangireddy SR, Hogaboam CM, Standiford TJ, Thannickal VJ, Reddy RC. PPAR-gamma agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 294: L891-L901, 2008.
23. Moustakas A, Souchelnytskyi S, Heldin CH. Smad regulation in TGFbeta signal transduction. J Cell Sci 114: 4359-4369, 2001.
24. Nisbet RE, Bland JM, Kleinhenz DJ, Mitchell PO, Walp ER, Sutliff RL, Hart CM. Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model. Am J Respir Crit Care Med 42: 482-490, 2009.
25. Nozell S, Laver T, Moseley D, Nowoslawski L, DeVos M, Atkinson GP, Harrison K, Nabors LB, Benveniste EN. The ING4 tumor suppressor attenuates NF-kappaB activity at the promoters of target genes. Mol Cell Biol 28: 6632-6645, 2008.
26. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 118: 2372-2379, 2008.
27. Selimovic N, Bergh CH, Andersson B, Sakiniene E, Carlsten H, Rundqvist B. Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension. Eur Respir J 34: 662-668, 2009.
28. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landstrom M. The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner. Nat Cell Biol 10: 1199-1207, 2008.
29. Thomas M, Docx C, Holmes AM, Beach S, Duggan N, England K, Leblanc C, Lebret C, Schindler F, Raza F, Walker C, Crosby A, Davies RJ, Morrell NW, Budd DC. Activin-like kinase 5 (ALK5) mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. Am J Pathol 174: 380-389, 2009.
30. Tuder RM, Abman SH, Braun T, Capron F, Stevens T, Thistlethwaite PA, Haworth SG. Development and pathology of pulmonary hypertension. J Am Coll Cardiol 54: S3-S9, 2009.
31. Xiong C, Mou Y, Zhang J, Fu M, Chen YE, Akinbami MA, Cui T. Impaired expression of PPARgamma protein contributes to the exaggerated growth of vascular smooth muscle cells in spontaneously hypertensive rats. Life Sci 77: 3037-3048, 2005.
32. Yuan JXJ, Ward JPT, Rabinovitch M. PPARγ and the pathobiology of pulmonary arterial hypertension. In: Membrane Receptors, Channels and Transporters in Pulmonary Circulation. New York, NY: Humana, 2010, p. 447-458.
33. Zheng S, Chen A. Disruption of transforming growth factor-β signaling by curcumin induces gene expression of peroxisome proliferator-activated receptor-γ in rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 292: G113-G123, 2007.