Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 398

Insulin-like Growth Factor and Partners

Insulin-like growth factor IGF2, IGF-binding protein IGFBP2 (but neither IGF1 nor
IGFBP1), and both IGF receptors IGFR1 and IGFR2 are produced in airway smooth
myocytes [ 732 ]. In addition, IGF2 and IGFBP2 are secreted.

Platelet-Derived Growth Factors

Platelet-derived growth factors (PDGF) are mitogens and recruitment factors for
smooth myocytes. Protomer PDGFb signals via the receptor protein Tyr kinase
PDGFR . 24 Protomers PDGFa and PDGFb are synthesized by various cell types,

including vascular smooth myocytes. Isotype PDGFa is required during the body's
development in the recruitment of smooth myocytes to alveolar sacs and their
compartmentation into alveoli [ 733 ]. Smooth myocytes express both PDGFR types,
but usually higher levels of PDGFR

β

β .

Vascular Endothelial Growth Factors

In humans, airway smooth myocyte synthesizes vascular endothelial growth factor
VEGFa isoforms, such as VEGFa 121 ,VEGFa 165 ,VEGFa 189 , and VEGFa 206 splice
variants [ 731 ]. The constitutive secretion of VEGFa increases on bradykinin
exposure, activation of B 2 bradykinin receptor and protein kinase-C, and generation
of prostanoids. Activated cyclooxygenase-2 produces predominantly prostaglandins
PGe2 and prostacyclin (PGi2). 25

8.4.4.3 Epican

Plasmalemmal CD44 glycoprotein, or epican, a heparan sulfate proteoglycan, is also
synthesized by airway smooth myocytes. This molecule interacts with hyaluronic
acid, collagens, and matrix metallopeptidases; its glycosylated form with fibrinogen
and fibrin; its sialyfucosylated glycoforms with selectins. Matrix metallopeptidase
MMP2 is an autocrine factor required for airway smooth myocyte proliferation.

24 During angiogenesis, sprouting tip endothelial cells secrete PDGFb that promotes recruitment of
PDGFR

vascular smooth myocytes to the endothelium.
25 Densities of VEGFR1, a modulator of VEGF activity, and VEGFR2, the active pro-angiogenic
receptor, increase in asthma [ 734 ]. Receptor VEGFR1 abounds on vascular smooth myocytes.
In addition, VEGF maintains alveolar cell survival, hence avoiding alveolar wall destruction
(emphysema) [ 735 ].

β+