iNOS‐derived nitric oxide mediates the increase in TFF2 expression associated with gastric damage: role of HIF‐1
2009; Wiley; Volume: 24; Issue: 1 Linguagem: Inglês
10.1096/fj.09-137489
ISSN1530-6860
AutoresD Ortiz‐Masiá, Carlos Hernández, Elsa Quintana, Miriam Veiázquez, Sonia Cebrián, Annia Riaño, Sara Calatayud, Juan V. Esplugues, M D Barrachina,
Tópico(s)Respiratory Support and Mechanisms
ResumoThe FASEB JournalVolume 24, Issue 1 p. 136-145 Research CommunicationFree to Read iNOS-derived nitric oxide mediates the increase in TFF2 expression associated with gastric damage: role of HIF-1 Dolores Ortiz-Masiá, Dolores Ortiz-Masiá Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorCarlos Hernández, Carlos Hernández CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorElsa Quintana, Elsa Quintana CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorMiriam Veiázquez, Miriam Veiázquez Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorSonia Cebrián, Sonia Cebrián CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorAnnia Riaño, Annia Riaño CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorSara Calatayud, Sara Calatayud Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorJuan V. Esplugues, Juan V. Esplugues Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorMaria D. Barrachina, Corresponding Author Maria D. Barrachina [email protected] Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainCorrespondence: Department of Pharmacology, Faculty of Medicine, University of Valencia, Avda. Blasco Ibáñez, 15–17, 46010 Valencia Spain. E-mail: [email protected]Search for more papers by this author Dolores Ortiz-Masiá, Dolores Ortiz-Masiá Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorCarlos Hernández, Carlos Hernández CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorElsa Quintana, Elsa Quintana CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorMiriam Veiázquez, Miriam Veiázquez Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorSonia Cebrián, Sonia Cebrián CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorAnnia Riaño, Annia Riaño CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorSara Calatayud, Sara Calatayud Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorJuan V. Esplugues, Juan V. Esplugues Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainSearch for more papers by this authorMaria D. Barrachina, Corresponding Author Maria D. Barrachina [email protected] Departamento de Farmacología, CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, SpainCorrespondence: Department of Pharmacology, Faculty of Medicine, University of Valencia, Avda. Blasco Ibáñez, 15–17, 46010 Valencia Spain. E-mail: [email protected]Search for more papers by this author First published: 09 September 2009 https://doi.org/10.1096/fj.09-137489Citations: 21 These authors contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT Trefoil (TFF) peptides are involved in gastrointestinal mucosal restitution. An hypoxia inducible factor 1 (HIF-l)-dependent induction of TFF genes has been reported in gastric epithelial cells. Nitric oxide (NO) is associated with mucosal damage and modulates HIF-1 activity. The aim of the present study was to analyze the role of iNOS-derived NO in HIF-1 α stabilization and TFF gene expression in damaged gastric mucosa. Aspirin caused gastric injury that peaked 6 h after dosing and returned to normality at 24 h. iNOS mRNA expression occurs in the corpus in parallel with damage. Blockade of iNOS activity did not modify gastric lesions induced by aspirin but delayed mucosal healing. Aspirin induced HIF-1α stabilization and TFF2 mRNA up-regulation in the mucosa, but these effects were diminished when iNOS activity was inhibited. Results obtained using a coculture setup showed that iNOS-derived NO from activated mac-rophages induced HIF-1 α stabilization, TFF gene expression' and accelerated wound healing in cultured epithelial cells. Finally, transient silencing of endogenous HIF-1α in epithelial cells significantly undermined activated mac-rophage-induced TFF gene expression. Evidence suggests that the iNOS-derived NO associated with NSAID-induced gastric injury is implicated in mucosal restitution via the HIF-1-mediated induction of TFF genes.—Ortiz-Masiá, D., Hernandez, C., Quintana, E., Velazquez, M., Cebrián, S., Riano, A., Calatayud, S., Esplugues, J. V., Barrachina, M. D. iNOS-derived nitric oxide mediates the increase in TFF2 expression associated with gastric damage: role of HIF-1. FASEB J. 24, 136–145 (2010). www.fasebj.org REFERENCES 1Sands, B. E., and Podolsky, D. K. (1996) The trefoil peptide family. Annu. Rev. Physiol. 58, 253–273 2Taupin, D., and Podolsky, D. K. (2003) Trefoil factors: initiators of mucosal healing. Nat. Rev. Mol. Cell. Biol. 4, 721–732 3Dignass, A., Lynch-Devaney, K., Kindon, H., Thim, L., and Podolsky, D. K. (1994) Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway. J. Clin. 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