Skip Navigation



Human Molecular Genetics Advance Access published online on August 22, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl234
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
15/19/2923    most recent
ddl234v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Vendelin, J.
Right arrow Articles by Kere, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vendelin, J.
Right arrow Articles by Kere, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved
Received July 5, 2006
Revised August 11, 2006
Accepted August 11, 2006

Article

Downstream target genes of the Neuropeptide S--NPSR1 pathway

Johanna Vendelin 1, Sara Bruce 2, Päivi Holopainen 3, Ville Pulkkinen 1, Paula Rytilä 4, Asta Pirskanen 5, Marko Rehn 5, Tarja Laitinen 5, Lauri A. Laitinen 6, Tari Haahtela 4, Ulpu Saarialho-Kere 7, Annika Laitinen 8, and Juha Kere 9 *

1 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
2 Department of Biosciences and Nutrition, Karolinska Institutet, and Clinical Research Centre, Karolinska University Hospital, Huddinge, Sweden
3 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; SIAF, Davos, Switzerland
4 Department of Allergy, Helsinki University Central Hospital, Helsinki, Finland
5 GeneOS Ltd., Helsinki, Finland
6 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
7 Department of Dermatology, University of Helsinki, Helsinki, Finland; Department of Dermatology, Karolinska Institutet at Stockholm Söder Hospital, Stockholm, Sweden
8 Department of Anatomy, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
9 Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, and Clinical Research Centre, Karolinska University Hospital, Huddinge, Sweden

* To whom correspondence should be addressed.
Juha Kere, E-mail: juha.kere{at}biosci.ki.se


  Abstract

The Neuropeptide S (NPS) - NPS Receptor 1 (NPSR1) pathway has recently been implicated in the pathogenesis of asthma. The purpose of this study was to identify downstream gene targets regulated by NPSR1 upon NPS stimulation. A total of 104 genes were found significantly up-regulated and 42 down-regulated by microarray analysis 6 h after NPS administration. By Gene Ontology enrichment analysis, the categories "cell proliferation", "morphogenesis" and "immune response" were among the most altered. A TMM microarray database comparison suggested a common co-regulated pathway, which includes JUN/FOS oncogene homologs; early growth response genes, nuclear receptor subfamily 4 members and dual specificity phosphatases. The expression of four up-regulated genes, matrix metallopeptidase 10 (MMP10), INHBA (activin A), interleukin 8 (IL8) and EPH receptor A2 (EPHA2), exhibited a significant NPS dose-response relationship as confirmed by quantitative reverse-transcriptase PCR and for MMP10 by immunoassay. Immunohistochemical analyses revealed that MMP10 and TIMP metallopeptidase inhibitor 3 (TIMP3) were both strongly expressed in bronchial epithelium, and macrophages and eosinophils expressed MMP10 in asthmatic sputum samples. Because remodelling of airway epithelium is a feature of chronic asthma, the up-regulation of MMP10 and TIMP3 by NPS-NPSR1 signaling may be of relevance in the pathogenesis of asthma.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
C. Orsmark-Pietras, E. Melen, J. Vendelin, S. Bruce, A. Laitinen, L. A. Laitinen, R. Lauener, J. Riedler, E. von Mutius, G. Doekes, et al.
Biological and genetic interaction between Tenascin C and Neuropeptide S receptor 1 in allergic diseases
Hum. Mol. Genet., June 1, 2008; 17(11): 1673 - 1682.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.