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Dual ERK and phosphatidylinositol 3-kinase pathways control airway smooth muscle proliferation: Differences in asthma.
- Source :
-
Journal of Cellular Physiology . Sep2008, Vol. 216 Issue 3, p673-679. 7p. 1 Black and White Photograph, 6 Graphs. - Publication Year :
- 2008
-
Abstract
- Hyperplasia of airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely due to increased muscle proliferation. We have shown that ASM cells obtained from asthmatic patients proliferate faster than those obtained from non-asthmatic patients. In ASM from non-asthmatics, mitogens act via dual signaling pathways (both ERK- and PI 3-kinase-dependent) to control growth. In this study we are the first to examine whether dual pathways control the enhanced proliferation of ASM from asthmatics. When cells were incubated with 0.1% or 1% FBS, ERK activation was significantly greater in cells from asthmatic subjects (P < 0.05). In contrast, when cells were stimulated with 10% FBS, ERK activity was significantly greater in the non-asthmatic cells. However, cell proliferation in asthmatic cells was still significantly higher in cells stimulated by both 1% and 10% FBS. Pharmacological inhibition revealed that although dual proliferative pathways control ASM growth in cells from non-asthmatics stimulated with 10% FBS to an equal extent ([3H]-thymidine incorporation reduced to 57.2 ± 6.9% by the PI 3-kinase inhibitor LY294002 and 57.8 ± 1.1% by the ERK-pathway inhibitor U0126); in asthmatics, the presence of a strong proliferative stimulus (10% FBS) reduces ERK activation resulting in a shift to the PI 3-kinase pathway. The underlying mechanism appears to be upregulation of an endogenous MAPK inhibitor—MKP-1—that constrains ERK signaling in asthmatic cells under strong mitogenic stimulation. This study suggests that the PI 3-kinase pathway may be an attractive target for reversing hyperplasia in asthma. J. Cell. Physiol. 216: 673–679, 2008, © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SMOOTH muscle
*ASTHMA
*CELL proliferation
*HYPERPLASIA
*THYMIDINE
*PROTEIN kinases
Subjects
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 216
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32750424
- Full Text :
- https://doi.org/10.1002/jcp.21450