Myosin, transgelin, and myosin light chain kinase: expression and function in asthma

Am J Respir Crit Care Med. 2009 Feb 1;179(3):194-204. doi: 10.1164/rccm.200609-1367OC. Epub 2008 Nov 14.

Abstract

Rationale: Airway smooth muscle (SM) of patients with asthma exhibits a greater velocity of shortening (Vmax) than that of normal subjects, and this is thought to contribute to airway hyperresponsiveness. A greater Vmax can result from increased myosin activation. This has been reported in sensitized human airway SM and in models of asthma. A faster Vmax can also result from the expression of specific contractile proteins that promote faster cross-bridge cycling. This possibility has never been addressed in asthma.

Objectives: We tested the hypothesis that the expression of genes coding for SM contractile proteins is altered in asthmatic airways and contributes to their increased Vmax.

Methods: We quantified the expression of several genes that code for SM contractile proteins in mild allergic asthmatic and control human airway endobronchial biopsies. The function of these contractile proteins was tested using the in vitro motility assay.

Measurements and main results: We observed an increased expression of the fast myosin heavy chain isoform, transgelin, and myosin light chain kinase in patients with asthma. Immunohistochemistry demonstrated the expression of these genes at the protein level. To address the functional significance of this overexpression, we purified tracheal myosin from the hyperresponsive Fisher rats, which also overexpress the fast myosin heavy chain isoform as compared with the normoresponsive Lewis rats, and found a faster rate of actin filament propulsion. Conversely, transgelin did not alter the rate of actin filament propulsion.

Conclusions: Selective overexpression of airway smooth muscle genes in asthmatic airways leads to increased Vmax, thus contributing to the airway hyperresponsiveness observed in asthma.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Animals
  • Asthma / genetics
  • Asthma / metabolism*
  • Asthma / pathology
  • Biopsy
  • Blotting, Western
  • Bronchoscopy
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Follow-Up Studies
  • Gene Expression*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Male
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / genetics*
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / genetics*
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth / pathology
  • Myosin Heavy Chains / biosynthesis
  • Myosin Heavy Chains / genetics*
  • Myosin-Light-Chain Kinase / biosynthesis
  • Myosin-Light-Chain Kinase / genetics*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics*
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Xenopus Proteins

Substances

  • Microfilament Proteins
  • Muscle Proteins
  • RNA, Messenger
  • Xenopus Proteins
  • transgelin
  • Myosin-Light-Chain Kinase
  • Myosin Heavy Chains