Biomedical Engineering Reference
In-Depth Information
8.4
Airway Smooth Myocytes
8.4.1
Mechanical Loading-Induced Cytoskeleton Remodeling
Airway smooth myocyte (aSMC) is able to modify its shape, stiffness, and contrac-
tility in response to mechanical loading after adaptation of actomyosin interaction
and integrins at adhesion junctions [ 718 ].
In the tracheal muscle, strains elevate phosphorylation level of both focal
adhesion kinase and paxillin. Once phosphorylated by focal adhesion kinase, ad-
hesion complex component paxillin couples to neuronal Wiskott-Aldrich syndrome
protein (nWASP) via CRK adaptor to launch nWASP activation by activated CDC42
GTPase that binds to recruited nWASP (Vol. 1 - Chaps. 6. Cell Cytoskeleton
and 7. Plasma Membrane). The latter stimulates the ARP2-ARP3 complex that
polymerizes actin filaments.
Integrin-linked kinase and its binding partners coordinate cytoskeleton
remodeling, especially formation of structural links between integrins and the actin
cytoskeleton. Integrin-linked kinase tethers to
β 1 -integrins and can then transduce
signals from integrin receptors to regulate actin polymerization. This scaffold forms
a heterotrimer with LIMS1 adaptor (or PINCH) and
-parvin that binds to actin
filaments. Enzyme ILK also connects to paxillin. In addition, LIMS1 adaptor may
couple to nWASP via NCK adaptor.
α
8.4.2
Contractile and Proliferative Phenotype
Airway smooth myocyte can evolve from a contractile to a proliferative phenotype.
When aSMCs proliferate, the content in smooth muscle
-actin, high-molecular-
weight caldesmon hMW isoform, calponin, desmin, smooth muscle myosin heavy
chain, myosin light chain kinase, and
α
-tropomyosin decays. On the other hand, the
content of non-muscle myosin heavy chain, low-molecular-weight caldesmon lMW ,
vimentin, protein kinase-C
β
, and CD44 heightens (1-6 fold) when cells
divide [ 719 ]. The content in cytoskeletal proteins is greater in the trachealis muscle
than that in the media of the pulmonary artery [ 719 ]. Airway smooth myocytes
shorten faster than arterial ones.
α
and -C
β
8.4.3
Calcium Influx
Plasma membrane depolarization activates Ca V channels. Subsequent Ca 2 + entry
causes rapidly (in a few milliseconds) local Ca 2 + release through ryanodine
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