The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.
Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0438c1ab1e9a44b9a5f63cce020f4d9f |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0438c1ab1e9a44b9a5f63cce020f4d9f |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0438c1ab1e9a44b9a5f63cce020f4d9f2021-11-18T08:42:58ZThe α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.1932-620310.1371/journal.pone.0080637https://doaj.org/article/0438c1ab1e9a44b9a5f63cce020f4d9f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349008/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ) mice). Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ) mice. CREB(αΔ) mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ) and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ). CREB(αΔ) mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.Lili LiKatherine HowellMichelle SandsMark BanahanStephen FrohlichSimon C RowanRoisín NearyDonal RyanPaul McLoughlinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e80637 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Lili Li Katherine Howell Michelle Sands Mark Banahan Stephen Frohlich Simon C Rowan Roisín Neary Donal Ryan Paul McLoughlin The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| description |
Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ) mice). Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ) mice. CREB(αΔ) mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ) and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ). CREB(αΔ) mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases. |
| format |
article |
| author |
Lili Li Katherine Howell Michelle Sands Mark Banahan Stephen Frohlich Simon C Rowan Roisín Neary Donal Ryan Paul McLoughlin |
| author_facet |
Lili Li Katherine Howell Michelle Sands Mark Banahan Stephen Frohlich Simon C Rowan Roisín Neary Donal Ryan Paul McLoughlin |
| author_sort |
Lili Li |
| title |
The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| title_short |
The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| title_full |
The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| title_fullStr |
The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| title_full_unstemmed |
The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. |
| title_sort |
α and δ isoforms of creb1 are required to maintain normal pulmonary vascular resistance. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/0438c1ab1e9a44b9a5f63cce020f4d9f |
| work_keys_str_mv |
AT lilili theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT katherinehowell theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT michellesands theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT markbanahan theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT stephenfrohlich theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT simoncrowan theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT roisinneary theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT donalryan theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT paulmcloughlin theaanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT lilili aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT katherinehowell aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT michellesands aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT markbanahan aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT stephenfrohlich aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT simoncrowan aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT roisinneary aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT donalryan aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance AT paulmcloughlin aanddisoformsofcreb1arerequiredtomaintainnormalpulmonaryvascularresistance |
| _version_ |
1718421362777784320 |