Role of gremlin in the lung: Development and disease

American Journal of Respiratory Cell and Molecular Biology

Volumn 42, Issue 5, 2010, Pages 517-523

  Costello, Christine M ^a   Cahill, Edwina ^a   Martin, Finian ^a   Gaine, Sean ^b   McLoughlin, Paul ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

^b MATER MISERICORDIAE UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Bone morphogenetic protein; Gremlin; Pulmonary hypertension

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR; CHORDIN; FOLLISTATIN; GLYCOPROTEIN; GREMLIN; NOGGIN; UNCLASSIFIED DRUG; SIGNAL PEPTIDE;

CELL ACTIVITY; GASTRULATION; HUMAN; LUNG DEVELOPMENT; LUNG DISEASE; LUNG FIBROSIS; MEDICAL RESEARCH; NONHUMAN; PATHOGENESIS; PULMONARY HYPERTENSION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; ANTIBODY SPECIFICITY; DRUG ANTAGONISM; LUNG; METABOLISM; PATHOLOGY; PRENATAL DEVELOPMENT;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS; BONE MORPHOGENETIC PROTEINS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LUNG; LUNG DISEASES; ORGAN SPECIFICITY;

EID: 77951645428     PISSN: 10441549     EISSN: None     Source Type: Journal    
DOI: 10.1165/rcmb.2009-0101TR     Document Type: Review

References (53)

1. Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1998;1:673-683. (Pubitemid 128379245)
2. Topol LZ, Bardot B, Zhang Q, Resau J, Huillard E, Marx M, Calothy G, Blair DG. Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin. J Biol Chem 2000;275:8785-8793.
3. Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 2006;7:51-65. (Pubitemid 46044349)
4. Balemans W, Van Hul W. Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev Biol 2002;250:231-250. (Pubitemid 35216412)
5. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233-241.
6. Wagner TU. Bone morphogenetic protein signaling in stem cells: one signal, many consequences. FEBS J 2007;274:2968-2976.
7. Maciel TT, Melo RS, Schor N, Campos AH. Gremlin promotes vascular smooth muscle cell proliferation and migration. J Mol Cell Cardiol 2008;44:370-379.
8. Nohe A, Keating E, Knaus P, Petersen NO. Signal transduction of bone morphogenetic protein receptors. Cell Signal 2004;16:291-299. (Pubitemid 37542404)
9. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, Sheares KK, Trembath RC. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation 2001;104:790-795. (Pubitemid 32762677)
10. Teichert-Kuliszewska K, Kutryk MJ, Kuliszewski MA, Karoubi G, Courtman DW, Zucco L, Granton J, Stewart DJ. Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension. Circ Res 2006;98:209-217. (Pubitemid 43755352)
11. Sun J, Zhuang FF, Mullersman JE, Chen H, Robertson EJ, Warburton D, Liu YH, Shi W. BMP4 activation and secretion are negatively regulated by an intracellular gremlin-BMP4 interaction. J Biol Chem 2006;281:29349-29356. (Pubitemid 44507078)
12. Chen B, Blair DG, Plisov S, Vasiliev G, Perantoni AO, Chen Q, Athanasiou M, Wu JY, Oppenheim JJ, Yang D. Cutting edge: bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with Slits and act as negative regulators of monocyte chemotaxis. J Immunol 2004;173:5914-5917. (Pubitemid 39487743)
13. Stabile H, Mitola S, Moroni E, Belleri M, Nicoli S, Coltrini D, Peri F, Pessi A, Orsatti L, Talamo F, et al. Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor. Blood 2007;109:1834-1840. (Pubitemid 46348177)
14. Lu MM, Yang H, Zhang L, Shu W, Blair DG, Morrisey EE. The bone morphogenic protein antagonist gremlin regulates proximal-distal patterning of the lung. Dev Dyn 2001;222:667-680.
15. Shi W, Zhao J, Anderson KD, Warburton D. Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol 2001;280:L1030-L1039.
16. Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development 2004;131:3401-3410.
17. Khokha MK, Hsu D, Brunet LJ, Dionne MS, Harland RM. Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat Genet 2003;34:303-307.
18. Gazzerro E, Pereira RC, Jorgetti V, Olson S, Economides AN, Canalis E. Skeletal overexpression of gremlin impairs bone formation and causes osteopenia. Endocrinology 2005;146:655-665.
19. Gazzerro E, Smerdel-Ramoya A, Zanotti S, Stadmeyer L, Durant D, Economides AN, Canalis E. Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. J Biol Chem 2007;282:31549-31557.
20. McMahon R, Murphy M, Clarkson M, Taal M, Mackenzie HS, Godson C, Martin F, Brady HR. IHG-2, a mesangial cell gene induced by high glucose, is human gremlin: regulation by extracellular glucose concentration, cyclic mechanical strain, and transforming growth factor-beta1. J Biol Chem 2000;275:9901-9904.
21. Dolan V, Murphy M, Sadlier D, Lappin D, Doran P, Godson C, Martin F, Oapos;Meara Y, Schmid H, Henger A, et al. Expression of gremlin, a bone morphogenetic protein antagonist, in human diabetic nephropathy. Am J Kidney Dis 2005;45:1034-1039.
22. Boers W, Aarrass S, Linthorst C, Pinzani M, Elferink RO, Bosma P. Transcriptional profiling reveals novel markers of liver fibrogenesis: gremlin and insulin-like growth factor-binding proteins. J Biol Chem 2006;281:16289-16295.
23. Hopkins N, McLoughlin P. The structural basis of pulmonary hypertension in chronic lung disease: remodelling, rarefaction or angiogenesis? J Anat 2002;201:335-348.
24. Costello CM, Howell K, Cahill E, McBryan J, Konigshoff M, Eickelberg O, Gaine S, Martin F, McLoughlin P. Lung-selective gene responses to alveolar hypoxia: potential role for the bone morphogenetic antagonist gremlin in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2008;295:L272-L284.
25. Wu W, Dave NB, Yu G, Strollo PJ, Kovkarova-Naumovski E, Ryter SW, Reeves SR, Dayyat E, Wang Y, Choi AMK, et al. Network analysis of temporal effects of intermittent and sustained hypoxia on rat lungs. Physiol Genomics 2008;36:24-34.
26. Kariyawasam HH, Xanthou G, Barkans J, Aizen M, Kay AB, Robinson DS. Basal expression of bone morphogenetic protein receptor is reduced in mild asthma. Am J Respir Crit Care Med 2008;177:1074-1081.
27. Koli K, Myllarniemi M, Vuorinen K, Salmenkivi K, Ryynanen MJ, Kinnula VL, Keski-Oja J. Bone morphogenetic protein-4 inhibitor gremlin is overexpressed in idiopathic pulmonary fibrosis. Am J Pathol 2006;169:61-71.
28. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA III, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 2000;26:81-84.
29. Durrington HJ, Morrell NW. What we know and what we would like to know about genetics and pulmonary arterial hypertension. Int J Clin Pract Suppl 2009;161:11-16.
30. Rabinovitch M. Pathobiology of pulmonary hypertension. Annu Rev Pathol 2007;2:369-399.
31. Eickelberg O, Morty RE. Transforming growth factor beta/bone morphogenic protein signaling in pulmonary arterial hypertension: remodeling revisited. Trends Cardiovasc Med 2007;17:263-269.
32. Hong KH, Lee YJ, Lee E, Park SO, Han C, Beppu H, Li E, Raizada MK, Bloch KD, Oh SP. Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 2008;118:722-730.
33. West J, Harral J, Lane K, Deng Y, Ickes B, Crona D, Albu S, Stewart DJ, Fagan K. Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 2008;295:L744-L755.
34. Takahashi K, Kogaki S, Matsushita T, Nasuno S, Kurotobi S, Ozono K. Hypoxia induces alteration of bone morphogenetic protein receptor signaling in pulmonary artery endothelial cell. Pediatr Res 2007;61:392-397.
35. Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, Remmelink M, Brimioulle S, Salmon I, Naeije R. Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 2005;289:H2319-H2324.
36. Morty RE, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri FM, Peters DM, Dumitrascu R, Seeger W, Knaus P, et al. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 2007;27:1072-1078.
37. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 2002;105:1672-1678. (Pubitemid 34298611)
38. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thistlethwaite PA. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003;348:500-509. (Pubitemid 36159885)
39. Leonard MO, Howell K, Madden SF, Costello CM, Higgins DG, Taylor CT, McLoughlin P. Hypoxia selectively activates the CREB family of transcription factors in the in vivo lung. Am J Respir Crit Care Med 2008;178:977-983.
40. Myllarniemi M, Vuorinen K, Pulkkinen V, Kankaanranta H, Aine T, Salmenkivi K, Keski-Oja J, Koli K, Kinnula V. Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype. J Pathol 2008;214:456-463.
41. Richter A, Yeager ME, Zaiman A, Cool CD, Voelkel NF, Tuder RM. Impaired transforming growth factor-beta signaling in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2004;170:1340-1348.
42. Southwood M, Jeffery TK, Yang X, Upton PD, Hall SM, Atkinson C, Haworth SG, Stewart S, Reynolds PN, Long L, et al. Regulation of bone morphogenetic protein signalling in human pulmonary vascular development. J Pathol 2008;214:85-95.
43. Jeffery TK, Upton PD, Trembath RC, Morrell NW. BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol Lung Cell Mol Physiol 2005;288:L370-L378.
44. Atkinson C, Stewart S, Imamura T, Trembath RC, Morrell NW. Immunolocalisation of BMPR-II and TGF-ss type I and II receptors in primary plexogenic pulmonary hypertension. J Heart Lung Transplant 2001;20:149.
45. Hong JH, Lee GT, Lee JH, Kwon SJ, Park SH, Kim SJ, Kim IY. Effect of bone morphogenetic protein-6 on macrophages. Immunology 2008;128:e442-e450.
46. Liu D, Hou J, Hu X, Wang X, Xiao Y, Mou Y, De Leon H. Neuronal chemorepellent Slit2 inhibits vascular smooth muscle cell migration by suppressing small GTPase Rac1 activation. Circ Res 2006;98:480-489.
47. Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, Atkinson C, Chen H, Trembath RC, Morrell NW. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 2005;96:1053-1063.
48. Myllarniemi M, Lindholm P, Ryynanen MJ, Kliment CR, Salmenkivi K, Keski-Oja J, Kinnula VL, Oury TD, Koli K. Gremlin-mediated decrease in bone morphogenetic protein signaling promotes pulmonary fibrosis. Am J Respir Crit Care Med 2008;177:321-329.
49. 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 2009;119:566-576.
50. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003;9:964-968.
51. Guo X, Wang XF. Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 2009;19:71-88.
52. Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 2005;16:251-263.
53. Nathan SD, Noble PW, Tuder RM. Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Respir Crit Care Med 2007;175:875-880.