Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a

Junaith Mohamed, Ameena Hajira, Zhenlin Li, Denise Paulin, Aladin M. Boriek

Research output: Contribution to journalArticle

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Abstract

Bronchial biopsies of asthmatic patients show a negative correlation 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 (ASMCs Des-/-) show hypertrophy and up-regulation microRNA-26a (miR-26a). Knockdown of miR-26a in ASMCs Des-/- inhibits hypertrophy, whereas enforced expression of miR-26a in ASMCs Des+/+induces hypertrophy. We identify that Egr1 (early growth responsive protein-1) activates miR-26a promoter via enhanced phosphorylation of Erk1/2 in ASMCs Des-/-. We show glycogen synthase kinase-3β (GSK-3β) as a target gene of miR-26a. Moreover, induction of ASMCs Des-/- 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.

Original languageEnglish (US)
Pages (from-to)43394-43404
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number50
DOIs
StatePublished - Dec 16 2011

Fingerprint

Desmin
MicroRNAs
Hypertrophy
Smooth Muscle
Muscle
Growth
Proteins
Smooth Muscle Myocytes
Glycogen Synthase Kinase 3
Homeostasis
Bearings (structural)
Lung Compliance
Phosphorylation
Biopsy
Weight-Bearing
Up-Regulation
Genes
Cells
Lung

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a. / Mohamed, Junaith; Hajira, Ameena; Li, Zhenlin; Paulin, Denise; Boriek, Aladin M.

In: Journal of Biological Chemistry, Vol. 286, No. 50, 16.12.2011, p. 43394-43404.

Research output: Contribution to journalArticle

Mohamed, Junaith ; Hajira, Ameena ; Li, Zhenlin ; Paulin, Denise ; Boriek, Aladin M. / Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 50. pp. 43394-43404.
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