Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-κB signaling pathway in smooth muscle cells

Junaith Mohamed, Aladin M. Boriek

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Muscle cells, including human airway smooth muscle cells (HASMCs) express ankyrin repeat protein 1 (Ankrd1), a member of ankyrin repeat protein family. Ankrd1 efficiently interacts with the type III intermediate filament desmin. Our earlier study showed that desmin is an intracellular load-bearing protein that influences airway compliance, lung recoil, and airway contractile responsiveness. These results suggest that Ankrd1 and desmin may play important roles on ASMC homeostasis. Here we show that small interfering (si)RNA-mediated knockdown of the desmin gene in HASMCs, recombinant HASMCs (re- HASMCs), up-regulates Ankrd1 expression. Moreover, loss of desmin in HASMCs increases the phosphorylation of Akt, inhibitor of κB kinase (IKK)-α, and inhibitor of κB (IκB)-α proteins, leading to NF-κB activation. Treatment of reHASMCs with Akt, IKKα, IκBα, or NF-κB inhibitor inhibits the loss of desmin-induced Ankrd1 up-regulation, suggesting Akt/NF-κB-mediated Ankrd1 regulation. Transfection of reHASMCs with siRNA specific for p50 or p65 corroborates the NF-κB-mediated Ankrd1 regulation. Luciferase reporter assays show that NF-κB directly binds on Ankrd1 promoter and up-regulates Ankrd1 levels. Overall, our data provide a new link between desmin and Ankrd1 regulation, which may be important for ASMC homeostasis.- Mohamed, J. S., Boriek, A. M. Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-κB signaling pathway in smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)757-765
Number of pages9
JournalFASEB Journal
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Desmin
Smooth Muscle Myocytes
Muscle
Up-Regulation
Cells
Ankyrin Repeat
Small Interfering RNA
Homeostasis
Bearings (structural)
Gene Knockdown Techniques
Lung Compliance
Phosphorylation
Proteins
Intermediate Filaments
Weight-Bearing
Luciferases
Muscle Cells
Transfection
Assays
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-κB signaling pathway in smooth muscle cells. / Mohamed, Junaith; Boriek, Aladin M.

In: FASEB Journal, Vol. 26, No. 2, 01.02.2012, p. 757-765.

Research output: Contribution to journalArticle

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