help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 23, 2004, doi:10.1165/rcmb.2003-0330OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0330OCv1
31/1/13    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Powell, R. M.
Right arrow Articles by Davies, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Powell, R. M.
Right arrow Articles by Davies, D. E.
American Journal of Respiratory Cell and Molecular Biology. Vol. 31, pp. 13-21, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0330OC

Original Article

The Splicing and Fate of ADAM33 Transcripts in Primary Human Airways Fibroblasts

Robert M. Powell, James Wicks, John W. Holloway, Stephen T. Holgate and Donna E. Davies

Brooke Laboratories, Division of Infection, Inflammation and Repair, School of Medicine, Southampton General Hospital, Southampton, United Kingdom

Address correspondence to: Robert M. Powell, The Brooke Laboratories, Level F, South Mailpoint 888, Southampton General Hospital, Southampton SO16 6YD, UK. E-mail: R.M.Powell{at}soton.ac.uk

The ADAM (A Disintegrin and Metalloprotease) family of Zn++-dependent metalloproteases are multidomain proteins involved in diverse cellular activities. Polymorphic variation in ADAM33 is strongly associated with asthma and bronchial hyperresponsiveness. Identification of those isoforms of ADAM33 that are expressed in airways is fundamental to dissecting the role of ADAM33 in asthma. Analysis of primary human airways fibroblasts has shown the presence of a number of alternatively spliced forms of ADAM33, including one encoding a putative secreted variant, and many transcripts lacking the metalloproteinase domain. The relative abundance of these transcripts has been quantified using reverse transcription real-time polymerase chain reaction, in both nuclear and cytoplasmic fractions of RNA. These results demonstrate that a number of splice variants of ADAM33 are transported into the cytoplasm. Ninety percent of ADAM33 mRNA is retained in the nucleus and the subtle differences in the composition of nuclear and cytoplasmic RNA suggest important events in the splicing and selection of ADAM33 transcripts. Western blot analysis confirmed that several protein isoforms of ADAM33 are expressed in primary airways fibroblasts. These findings demonstrate that ADAM33 exists in multiple isoforms, suggesting that it is a complex molecule that plays multiple roles within mesenchymal cells.

Abbreviations: A Disintegrin and Metalloprotease, ADAM • bronchial hyperresponsiveness, BHR • epidermal growth factor, EGF • human airways fibroblasts, HAF • metalloproteinase, MP • polymerase chain reaction, PCR • single nucleotide polymorphism, SNP




This article has been cited by other articles:


Home page
 Eur Respir JHome page
H. M. Haitchi, H. Yoshisue, A. Ribbene, S. J. Wilson, J. W. Holloway, F. Bucchieri, N. A. Hanley, D. I. Wilson, G. Zummo, S. T. Holgate, et al.
Chronological expression of Ciliated Bronchial Epithelium 1 during pulmonary development
Eur. Respir. J., May 1, 2009; 33(5): 1095 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
S. T. Holgate, D. E. Davies, R. M. Powell, P. H. Howarth, H. M. Haitchi, and J. W. Holloway
Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms
Eur. Respir. J., April 1, 2007; 29(4): 793 - 803.
[Abstract] [Full Text] [PDF]

Home page
 Postgrad. Med. J.Home page
F. Sampsonas, A. Kaparianos, D. Lykouras, K. Karkoulias, and K. Spiropoulos
DNA sequence variations of metalloproteinases: their role in asthma and COPD
Postgrad. Med. J., April 1, 2007; 83(978): 244 - 250.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
S. T. Holgate, Y. Yang, H.-M. Haitchi, R. M. Powell, J. W. Holloway, H. Yoshisue, Y. Y. Pang, J. Cakebread, and D. E. Davies
The Genetics of Asthma: ADAM33 as an Example of a Susceptibility Gene.
Proceedings of the ATS, July 1, 2006; 3(5): 440 - 443.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J.-Y. Lee, S.-W. Park, H. K. Chang, H. Y. Kim, T. Rhim, J.-H. Lee, A.-S. Jang, E.-S. Koh, and C.-S. Park
A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma: Relevance to Airflow Limitation
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 729 - 735.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C. Boxall, S. T. Holgate, and D. E. Davies
The contribution of transforming growth factor-{beta} and epidermal growth factor signalling to airway remodelling in chronic asthma
Eur. Respir. J., January 1, 2006; 27(1): 208 - 229.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
Spoken sessions
Thorax, December 1, 2005; 60(suppl_2): ii4 - ii52.
[Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
J. Kere
Mapping and identifying genes for asthma and psoriasis
Phil Trans R Soc B, August 29, 2005; 360(1460): 1551 - 1561.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
S R Johnson
TIMP-1 in asthma: guilty by association
Thorax, August 1, 2005; 60(8): 617 - 618.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. C. van Diemen, D. S. Postma, J. M. Vonk, M. Bruinenberg, J. P. Schouten, and H. M. Boezen
A Disintegrin and Metalloprotease 33 Polymorphisms and Lung Function Decline in the General Population
Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 329 - 333.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Simpson, N. Maniatis, F. Jury, J. A. Cakebread, L. A. Lowe, S. T. Holgate, A. Woodcock, W. E. R. Ollier, A. Collins, A. Custovic, et al.
Polymorphisms in A Disintegrin and Metalloprotease 33 (ADAM33) Predict Impaired Early-Life Lung Function
Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 55 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. M. Haitchi, R. M. Powell, T. J. Shaw, P. H. Howarth, S. J. Wilson, D. I. Wilson, S. T. Holgate, and D. E. Davies
ADAM33 Expression in Asthmatic Airways and Human Embryonic Lungs
Am. J. Respir. Crit. Care Med., May 1, 2005; 171(9): 958 - 965.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
S T Holgate and J W Holloway
Is big beautiful? The continuing story of ADAM33 and asthma
Thorax, April 1, 2005; 60(4): 263 - 264.
[Full Text] [PDF]

Home page
 ThoraxHome page
J Blakey, E Halapi, U S Bjornsdottir, A Wheatley, S Kristinsson, R Upmanyu, K Stefansson, H Hakonarson, and I P Hall
Contribution of ADAM33 polymorphisms to the population risk of asthma
Thorax, April 1, 2005; 60(4): 274 - 276.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
H. Yoshisue, S. M. Puddicombe, S. J. Wilson, H. M. Haitchi, R. M. Powell, D. I. Wilson, A. Pandit, A. E. Berger, D. E. Davies, S. T. Holgate, et al.
Characterization of Ciliated Bronchial Epithelium 1, a Ciliated Cell-Associated Gene Induced During Mucociliary Differentiation
Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 491 - 500.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. A. Raby and S. T. Weiss
ADAM33: Where Are We Now?
Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 1 - 2.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society. 		  New Orleans Int'l Conf