Biomedical Engineering Reference
In-Depth Information
development. TGF-β exists in three known subtypes in humans, TGF-β1,
TGF-β2, and TGF-β3. These are upregulated in Marfan's syndrome [14]
and some human cancers, and they play crucial roles in tissue regenera-
tion, cell differentiation, embryonic development, and regulation of the
immune system. Isoforms of TGF-β1 are also thought to be involved in the
pathogenesis of preeclampsia (a medical condition in which hypertension
arises in pregnancy in association with significant amounts of protein in
the urine).
The TGF-β superfamily of cytokines includes the structurally related sub-
family of TGF-betas; the subfamily of bone morphogenic proteins (BMPs),
decapentaplegic (dpp) and Vg1; the subfamily of Mullerian inhibitory sub-
stances; and the subfamily of activins and inhibins. BMP induces ectopic
bone formation and plays an important role in the development of the vis-
cera. Ligand binding to its receptor induces the formation of a complex with
the type II BMP receptor phosphorylates and activates the type I BMP recep-
tor. The type I BMP receptor then propagates the signal by phosphorylating
a family of signal transducers, the SMAD proteins. Currently, eight SMAD
proteins have been cloned (SMAD1-7 and SMAD9). Upon phosphorylation
by BMP type I receptor, SMAD1 can interact with either SMAD4 or SMAD6.
The SMAD1-SMAD6 complex is inactive; the SMAD1-SMAD4 complex,
however, triggers the expression of BMP-responsive genes. The ratio between
SMAD4 and SMAD6 in cells can modulate the strength of the signal trans-
duced by BMP.
1.6.6 Platelet-Derived Growth Factor
According to Wikipedia, PDGF is one of the numerous growth factors—or
proteins that regulate cell growth and division—in bone metabolism. In par-
ticular, PDGF plays a significant role in blood vessel formation (angiogen-
esis), the growth of blood vessels from already existing blood vessel tissue.
Uncontrolled angiogenesis is a characteristic of cancer. In chemical terms,
platelet-derived growth factor is dimeric glycoprotein composed of two A
(-AA) or two B (-BB) chains or a combination of the two (-AB). PDGF is a
potent mitogen for cells of mesenchymal origin, including smooth muscle
cells and glial cells. In both mouse and human, the PDGF signaling net-
work consists of four ligands, PDGFA-D, and two receptors, PDGFRα and
PDGFRβ. All PDGFs function as secreted, disulfide-linked homodimers, but
only PDGFA and -B can form functional heterodimers.
PDGFs are mitogenic during early developmental stages, driving the
proliferation of undifferentiated mesenchyme and some progenitor popu-
lations. During later maturation stages, PDGF signaling has been impli-
cated in tissue remodeling and cellular differentiation, and in inductive
events involved in patterning and morphogenesis. In addition to driving
mesenchymal proliferation, PDGFs have been shown to direct the migra-
tion, differentiation, and function of a variety of specialized mesenchymal
