Paul D Upton

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. ncbi request reprint Functional characterization of bone morphogenetic protein binding sites and Smad1/5 activation in human vascular cells
    Paul D Upton
    Department of Medicine, Box 157, Level 5, Addenbrooke s Hospital, Cambridge, United Kingdom
    Mol Pharmacol 73:539-52. 2008
  2. doi request reprint TGF-beta and BMPR-II pharmacology--implications for pulmonary vascular diseases
    Paul D Upton
    University of Cambridge, Department of Medicine, Cambridge CB2 2QQ, United Kingdom
    Curr Opin Pharmacol 9:274-80. 2009
  3. pmc Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells
    Paul D Upton
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, UK
    J Biol Chem 284:15794-804. 2009
  4. doi request reprint The transforming growth factor-β-bone morphogenetic protein type signalling pathway in pulmonary vascular homeostasis and disease
    Paul D Upton
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Exp Physiol 98:1262-6. 2013
  5. ncbi request reprint Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension
    Xudong Yang
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Circ Res 96:1053-63. 2005
  6. doi request reprint Mutations in bone morphogenetic protein type II receptor cause dysregulation of Id gene expression in pulmonary artery smooth muscle cells: implications for familial pulmonary arterial hypertension
    Jun Yang
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, United Kingdom
    Circ Res 102:1212-21. 2008
  7. doi request reprint 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
    Lu Long
    Division of Respiratory Medicine, Department of Medicine, Box 157, Addenbrooke s Hospital, Hills Rd, Cambridge CB2 2QQ, United Kingdom
    Circulation 119:566-76. 2009
  8. ncbi request reprint Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension
    Nung Rudarakanchana
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, UK
    Hum Mol Genet 11:1517-25. 2002
  9. ncbi request reprint BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways
    Trina K Jeffery
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, CB2 2QQ, UK
    Am J Physiol Lung Cell Mol Physiol 288:L370-8. 2005
  10. doi request reprint Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue
    Anastasia Sobolewski
    Department of Medicine, University of Cambridge School of Clinical Medicine, Box 157, Addenbrooke s Hospital, Hills Road, Cambridge, Cambridgeshire CB2 2QQ, UK
    Hum Mol Genet 17:3180-90. 2008

Collaborators

Detail Information

Publications22

  1. ncbi request reprint Functional characterization of bone morphogenetic protein binding sites and Smad1/5 activation in human vascular cells
    Paul D Upton
    Department of Medicine, Box 157, Level 5, Addenbrooke s Hospital, Cambridge, United Kingdom
    Mol Pharmacol 73:539-52. 2008
    ..These cell-specific differences in BMP responses are important for understanding the pathogenesis of FPAH...
  2. doi request reprint TGF-beta and BMPR-II pharmacology--implications for pulmonary vascular diseases
    Paul D Upton
    University of Cambridge, Department of Medicine, Cambridge CB2 2QQ, United Kingdom
    Curr Opin Pharmacol 9:274-80. 2009
    ..We address the possible contribution of inflammation in disease progression and focus on potential emerging therapeutic targets...
  3. pmc Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells
    Paul D Upton
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, UK
    J Biol Chem 284:15794-804. 2009
    ..This differential signaling may contribute to the contrasting pathologies of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension...
  4. doi request reprint The transforming growth factor-β-bone morphogenetic protein type signalling pathway in pulmonary vascular homeostasis and disease
    Paul D Upton
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Exp Physiol 98:1262-6. 2013
    ....
  5. ncbi request reprint Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension
    Xudong Yang
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Circ Res 96:1053-63. 2005
    ..We conclude that defective Smad signaling and unopposed p38(MAPK)/ERK signaling, as a consequence of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed in familial PAH...
  6. doi request reprint Mutations in bone morphogenetic protein type II receptor cause dysregulation of Id gene expression in pulmonary artery smooth muscle cells: implications for familial pulmonary arterial hypertension
    Jun Yang
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, United Kingdom
    Circ Res 102:1212-21. 2008
    ..The integration of these signals at the level of Id gene expression may contribute to the pathogenesis of familial pulmonary arterial hypertension...
  7. doi request reprint 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
    Lu Long
    Division of Respiratory Medicine, Department of Medicine, Box 157, Addenbrooke s Hospital, Hills Rd, Cambridge CB2 2QQ, United Kingdom
    Circulation 119:566-76. 2009
    ..It remains unclear whether alterations in these pathways contribute to other forms of pulmonary hypertension and to what extent these changes can be exploited for therapeutic intervention...
  8. ncbi request reprint Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension
    Nung Rudarakanchana
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge CB2 2QQ, UK
    Hum Mol Genet 11:1517-25. 2002
    ..However, all mutants studied demonstrate a gain of function involving upregulation of p38(MAPK)-dependent proproliferative pathways...
  9. ncbi request reprint BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways
    Trina K Jeffery
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, CB2 2QQ, UK
    Am J Physiol Lung Cell Mol Physiol 288:L370-8. 2005
    ....
  10. doi request reprint Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue
    Anastasia Sobolewski
    Department of Medicine, University of Cambridge School of Clinical Medicine, Box 157, Addenbrooke s Hospital, Hills Road, Cambridge, Cambridgeshire CB2 2QQ, UK
    Hum Mol Genet 17:3180-90. 2008
    ..We conclude that enhancement of cell-surface trafficking of mutant and wild-type BMPR-II may have therapeutic potential in familial PAH...
  11. pmc BMP type II receptor deficiency confers resistance to growth inhibition by TGF-β in pulmonary artery smooth muscle cells: role of proinflammatory cytokines
    Rachel J Davies
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Am J Physiol Lung Cell Mol Physiol 302:L604-15. 2012
    ..Our study provides a rationale to test anti-interleukin therapies as an intervention to neutralize this inappropriate response and restore the antiproliferative response to TGF-β1...
  12. pmc The lysosomal inhibitor, chloroquine, increases cell surface BMPR-II levels and restores BMP9 signalling in endothelial cells harbouring BMPR-II mutations
    Benjamin J Dunmore
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge, UK
    Hum Mol Genet 22:3667-79. 2013
    ..These findings provide support for the restoration of cell surface BMPR-II with agents such as chloroquine as a potential therapeutic approach for heritable PAH. ..
  13. pmc Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II
    Hannah J Durrington
    From theDepartment of Medicine, University of Cambridge School of Clinical Medicine, Box 157, Addenbrooke s Hospital, Hills Road, Cambridge, Cambridgeshire CB2 0QQ, United Kingdom
    J Biol Chem 285:37641-9. 2010
    ..Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease...
  14. ncbi request reprint Eotaxin-1/CC chemokine ligand 11: a novel eosinophil survival factor secreted by human pulmonary artery endothelial cells
    Neda Farahi
    Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge, UK
    J Immunol 179:1264-73. 2007
    ..Furthermore, chemokine Ab arrays demonstrated up-regulation of CCL11 in HPAEC-CM. These data demonstrate the capacity of HPAECs to generate CCR3 agonists and the ability of CCL11 to inhibit human eosinophil apoptosis...
  15. ncbi request reprint Hypoxic induction of cox-2 regulates proliferation of human pulmonary artery smooth muscle cells
    Xudong Yang
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospitals, Cambridge, UK
    Am J Respir Cell Mol Biol 27:688-96. 2002
    ..In both cell types hypoxia modulates cell proliferation by induction of COX-2 and production of antiproliferative prostaglandins. Induction of COX-2 may contribute to the inhibition of hypoxia-induced pulmonary vascular remodeling...
  16. doi request reprint Transforming growth factor-β(1) represses bone morphogenetic protein-mediated Smad signaling in pulmonary artery smooth muscle cells via Smad3
    Paul D Upton
    1 Division of Respiratory Medicine, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, United Kingdom
    Am J Respir Cell Mol Biol 49:1135-45. 2013
    ..TGF-β1 reduces BMP4 signaling in PASMCs, a response that is exacerbated on the background of reduced BMP responsiveness due to BMPR-II mutations. These data provide a rationale for therapeutic inhibition of TGF-β1 signaling in PAH. ..
  17. ncbi request reprint Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor
    Carl Atkinson
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge, UK
    Circulation 105:1672-8. 2002
    ..Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-beta (TGF-beta) superfamily, underlie many familial and sporadic cases of primary pulmonary hypertension (PPH)...
  18. ncbi request reprint Does BMPR2 mutation disrupt pulmonary vasculogenesis?
    Trina K Jeffery
    Department of Medicine, Addenbrooke s Hospital, Cambridge, CB2 2QQ, UK
    Chest 128:602S. 2005
  19. ncbi request reprint Mechanism of cicaprost-induced desensitization in rat pulmonary artery smooth muscle cells involves a PKA-mediated inhibition of adenylyl cyclase
    Anastasia Sobolewski
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Cambridge CB2 2QQ, United Kingdom
    Am J Physiol Lung Cell Mol Physiol 287:L352-9. 2004
    ..Our data suggest that heterologous G(s)alpha desensitization by cicaprost is mediated predominantly by a PKA-inhibitable isoform of AC, most likely AC5/6...
  20. ncbi request reprint Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis
    Katy I Mecklenburgh
    Respiratory Medicine Division, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s and Papworth Hospitals, Cambridge, United Kingdom
    Blood 100:3008-16. 2002
    ..This finding may have important implications for the resolution of granulocytic inflammation at sites of low-oxygen tension...
  21. doi request reprint Transcript analysis reveals a specific HOX signature associated with positional identity of human endothelial cells
    Mark Toshner
    Department of Medicine, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom Papworth Hospital, Cambridge, United Kingdom
    PLoS ONE 9:e91334. 2014
    ..Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity. ..
  22. ncbi request reprint ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells
    Neil Davie
    Section on Clinical Pharmacology, Department of Histochemistry, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK
    Am J Respir Crit Care Med 165:398-405. 2002
    ..In conclusion, ET(A) and ET(B) receptors are differentially distributed in human pulmonary arteries. Both receptors promote the proliferation of PASMCs in vitro and may contribute to vascular remodeling in pulmonary hypertension...