p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway

  1. Sachs, Benjamin D.
  2. Baillie, George S.
  3. McCall, Julianne R.
  4. Passino, Melissa A.
  5. Schachtrup, Christian
  6. Wallace, Derek A.
  7. Dunlop, Allan J.
  8. MacKenzie, Kirsty F.
  9. Klussmann, Enno
  10. Lynch, Martin J.
  11. Sikorski, Shoana L.
  12. Nuriel, Tal
  13. Tsigelny, Igor
  14. Zhang, Jin
  15. Houslay, Miles D.
  16. Chao, Moses V.
  17. Akassoglou, Katerina

WeightNameValue
1000 Titel
  • p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway
1000 Autor/in
  1. Sachs, Benjamin D. |
  2. Baillie, George S. |
  3. McCall, Julianne R. |
  4. Passino, Melissa A. |
  5. Schachtrup, Christian |
  6. Wallace, Derek A. |
  7. Dunlop, Allan J. |
  8. MacKenzie, Kirsty F. |
  9. Klussmann, Enno |
  10. Lynch, Martin J. |
  11. Sikorski, Shoana L. |
  12. Nuriel, Tal |
  13. Tsigelny, Igor |
  14. Zhang, Jin |
  15. Houslay, Miles D. |
  16. Chao, Moses V. |
  17. Akassoglou, Katerina |
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2007-06-17
1000 Erschienen in
1000 Quellenangabe
  • 177(6): 1119-1132
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064370/ |
  • https://doi.org/10.1083/jcb.200701040 |
1000 Ergänzendes Material
  • http://jcb.rupress.org/content/177/6/1119/tab-figures-data |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Clearance of fibrin through proteolytic degradation is a critical step of matrix remodeling that contributes to tissue repair in a variety of pathological conditions, such as stroke, atherosclerosis, and pulmonary disease. However, the molecular mechanisms that regulate fibrin deposition are not known. Here, we report that the p75 neurotrophin receptor (p75NTR), a TNF receptor superfamily member up-regulated after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1). We have discovered a new mechanism in which phosphodiesterase PDE4A4/5 interacts with p75NTR to enhance cAMP degradation. The p75NTR-dependent down-regulation of cAMP results in a decrease in extracellular proteolytic activity. This mechanism is supported in vivo in p75NTR-deficient mice, which show increased proteolysis after sciatic nerve injury and lung fibrosis. Our results reveal a novel pathogenic mechanism by which p75NTR regulates degradation of cAMP and perpetuates scar formation after injury.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/U2FjaHMsIEJlbmphbWluIEQu|https://frl.publisso.de/adhoc/creator/QmFpbGxpZSwgR2VvcmdlIFMu|https://frl.publisso.de/adhoc/creator/TWNDYWxsLCBKdWxpYW5uZSBSLg==|https://frl.publisso.de/adhoc/creator/UGFzc2lubywgTWVsaXNzYSBBLg==|https://frl.publisso.de/adhoc/creator/U2NoYWNodHJ1cCwgQ2hyaXN0aWFu|https://frl.publisso.de/adhoc/creator/V2FsbGFjZSwgRGVyZWsgQS4=|https://frl.publisso.de/adhoc/creator/RHVubG9wLCBBbGxhbiBKLg==|https://frl.publisso.de/adhoc/creator/TWFjS2VuemllLCBLaXJzdHkgRi4=|https://frl.publisso.de/adhoc/creator/S2x1c3NtYW5uLCBFbm5v|https://frl.publisso.de/adhoc/creator/THluY2gsIE1hcnRpbiBKLg==|https://frl.publisso.de/adhoc/creator/U2lrb3Jza2ksIFNob2FuYSBMLg==|https://frl.publisso.de/adhoc/creator/TnVyaWVsLCBUYWw=|https://frl.publisso.de/adhoc/creator/VHNpZ2VsbnksIElnb3I=|https://frl.publisso.de/adhoc/creator/WmhhbmcsIEppbg==|https://frl.publisso.de/adhoc/creator/SG91c2xheSwgTWlsZXMgRC4=|https://frl.publisso.de/adhoc/creator/Q2hhbywgTW9zZXMgVi4=|https://frl.publisso.de/adhoc/creator/QWthc3NvZ2xvdSwgS2F0ZXJpbmE=
1000 Label
1000 Fördernummer
  1. 5T32-GM07752; NS27177; NS21072; HD23315; NS51470; NS52189
1000 Förderprogramm
  1. Pharmacology training grant
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6406503.rdf
1000 Erstellt am 2018-01-25T18:28:18.507+0100
1000 Erstellt von 218
1000 beschreibt frl:6406503
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet Thu Aug 18 07:43:30 CEST 2022
1000 Objekt bearb. Thu Apr 01 10:04:26 CEST 2021
1000 Vgl. frl:6406503
1000 Oai Id
  1. oai:frl.publisso.de:frl:6406503 |
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