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Desmin Regulates Airway Smooth Muscle Hypertrophy through Early Growth-responsive Protein-1 and MicroRNA-26a.
- Source :
-
Journal of Biological Chemistry . 12/16/2011, Vol. 286 Issue 50, p43394-43404. 11p. - Publication Year :
- 2011
-
Abstract
- Bronchial biopsies of asthmatic patients show a negative correlation between desmin expression in airway smooth muscle cell (ASMC) and airway hyperresponsiveness. We previously showed that desmin is an intracellular load-bearing protein, which influences airway compliance, lung recoil, and airway contractile responsiveness (Shardonofsky, F. R., Capetanaki, Y., and Boriek, A. M. (2006) Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L890-L896). These results suggest that desmin may play an important role in ASMC homeostasis. Here, we report that ASMCs of desmin null mice (ASMCsDes-/-) show hypertrophy and up-regulation microRNA-26a (miR-26a). Knockdown of miR-26a in ASMCsDes-/- inhibits hypertrophy, whereas enforced expression of miR-26a in ASMCsDes+/+ induces hypertrophy. We identify that Egr1 (early growth responsive protein-1) activates miR-26a promoter via enhanced phosphorylation of Erk1/2 in ASMCsDes-/-. We show glycogen synthase kinase-3β (GSK-3β) as a target gene of miR-26a. Moreover, induction of ASMCsDes-/- hypertrophy by the Erk-1/2/Egr-1/miR-26a/GSK-3β pathway is consistent in human recombinant ASMCs, which stably suppresses 90% endogenous desmin expression. Overall, our data demonstrate a novel role for desmin as an anti-hypertrophic protein necessary for ASMC homeostasis and identifies desmin as a novel regulator of microRNA. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HYPERTROPHY
*SMOOTH muscle
*AIRWAY (Anatomy)
*MICRORNA
*HOMEOSTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 286
- Issue :
- 50
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 70216524
- Full Text :
- https://doi.org/10.1074/jbc.M111.235127