cFLIP expression is altered in severe corticosteroid-resistant asthma
Dysregulation of alternative splicing of mRNA precursors is known to contribute to numerous human diseases. In this study we carried out the first systematic search for asthma-associated changes in alternative splicing events, using a model of Aspergillus fumigatus (A. fumigatus)-sensitized mice and...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-12-01
|
| Series: | Genomics Data |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213596014000233 |
| _version_ | 1828836965987909632 |
|---|---|
| author | Dennis Lazarev Rachel L. Miller Emily Dimango Xian-Dong Fu Hai-Ri Li Charlotte J. Logan James L. Manley |
| author_facet | Dennis Lazarev Rachel L. Miller Emily Dimango Xian-Dong Fu Hai-Ri Li Charlotte J. Logan James L. Manley |
| author_sort | Dennis Lazarev |
| collection | DOAJ |
| description | Dysregulation of alternative splicing of mRNA precursors is known to contribute to numerous human diseases. In this study we carried out the first systematic search for asthma-associated changes in alternative splicing events, using a model of Aspergillus fumigatus (A. fumigatus)-sensitized mice and an exon junction microarray to detect potential changes in alternative splicing. One of the sensitization-associated changes identified in the search was a shift in alternative splicing of the mRNA encoding cFLIP, a modulator of the caspase-mediated extrinsic apoptosis pathway. Expanding these studies to human asthma patients, we discovered a significant decrease in the expression of both cFLIP isoforms in severe corticosteroid-resistant asthmatics. Although it is unclear whether these changes were due solely to differences in alternative splicing, these findings provide evidence that dysregulation of the extrinsic apoptosis pathway is part of the underlying immunopathogenesis of severe refractory asthma. |
| first_indexed | 2024-12-12T18:33:02Z |
| format | Article |
| id | doaj.art-8cf8adb611974144821cc460181e02fe |
| institution | Directory Open Access Journal |
| issn | 2213-5960 |
| language | English |
| last_indexed | 2024-12-12T18:33:02Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Genomics Data |
| spelling | doaj.art-8cf8adb611974144821cc460181e02fe2022-12-22T00:15:52ZengElsevierGenomics Data2213-59602014-12-012C9910410.1016/j.gdata.2014.05.003cFLIP expression is altered in severe corticosteroid-resistant asthmaDennis Lazarev0Rachel L. Miller1Emily Dimango2Xian-Dong Fu3Hai-Ri Li4Charlotte J. Logan5James L. Manley6Department of Biological Sciences, Columbia University, New York, NY 10027, USADivision of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University, New York, NY 10032, USADivision of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University, New York, NY 10032, USADepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USADepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USACold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USADepartment of Biological Sciences, Columbia University, New York, NY 10027, USADysregulation of alternative splicing of mRNA precursors is known to contribute to numerous human diseases. In this study we carried out the first systematic search for asthma-associated changes in alternative splicing events, using a model of Aspergillus fumigatus (A. fumigatus)-sensitized mice and an exon junction microarray to detect potential changes in alternative splicing. One of the sensitization-associated changes identified in the search was a shift in alternative splicing of the mRNA encoding cFLIP, a modulator of the caspase-mediated extrinsic apoptosis pathway. Expanding these studies to human asthma patients, we discovered a significant decrease in the expression of both cFLIP isoforms in severe corticosteroid-resistant asthmatics. Although it is unclear whether these changes were due solely to differences in alternative splicing, these findings provide evidence that dysregulation of the extrinsic apoptosis pathway is part of the underlying immunopathogenesis of severe refractory asthma.http://www.sciencedirect.com/science/article/pii/S2213596014000233AsthmaAlternative splicingMicroarrays |
| spellingShingle | Dennis Lazarev Rachel L. Miller Emily Dimango Xian-Dong Fu Hai-Ri Li Charlotte J. Logan James L. Manley cFLIP expression is altered in severe corticosteroid-resistant asthma Genomics Data Asthma Alternative splicing Microarrays |
| title | cFLIP expression is altered in severe corticosteroid-resistant asthma |
| title_full | cFLIP expression is altered in severe corticosteroid-resistant asthma |
| title_fullStr | cFLIP expression is altered in severe corticosteroid-resistant asthma |
| title_full_unstemmed | cFLIP expression is altered in severe corticosteroid-resistant asthma |
| title_short | cFLIP expression is altered in severe corticosteroid-resistant asthma |
| title_sort | cflip expression is altered in severe corticosteroid resistant asthma |
| topic | Asthma Alternative splicing Microarrays |
| url | http://www.sciencedirect.com/science/article/pii/S2213596014000233 |
| work_keys_str_mv | AT dennislazarev cflipexpressionisalteredinseverecorticosteroidresistantasthma AT rachellmiller cflipexpressionisalteredinseverecorticosteroidresistantasthma AT emilydimango cflipexpressionisalteredinseverecorticosteroidresistantasthma AT xiandongfu cflipexpressionisalteredinseverecorticosteroidresistantasthma AT hairili cflipexpressionisalteredinseverecorticosteroidresistantasthma AT charlottejlogan cflipexpressionisalteredinseverecorticosteroidresistantasthma AT jameslmanley cflipexpressionisalteredinseverecorticosteroidresistantasthma |