Mechanosensory Pathways in Angiocrine Mediated Tissue Regeneration - Mechanical and Chemical Signaling in Angiogenesis - page 21

other factors, such as insulin, growth hormone (GH), bile acids, vasopressin
(AVP), platelet-derived serotonin, and endothelial growth factor (EGF) from the
blood. These factors cooperate with prostaglandins, heparin-binding EGF-like
growth factor, hepatic growth factor, as well as insulin-like growth factor-1.
Tumor growth factor and amphiregulin from different hepatic cells block the G1 to
M transition of the cell cycle.
Hepatic Stem Cells (HSCs) have the ability to inhibit G1 to S transition [ 15 , 16 ].
TGF-beta signaling is thus blocked during cell proliferation. Pro-Nerve Growth
Factor (Pro-NGF) and NGF, produced by regenerating hepatocytes, are able to
trigger apoptosis in activated TGF-producing HSCs. Once the liver has reached its
original mass, several factors (including activin A) are responsible for triggering the
end of liver regeneration.
The liver sinusoidal vasculature is lined with endothelial cells (SECs) that
distribute hepatic blood flow into each lobe. It is well known that occlusion of one
particular branch of the portal vein system results in an atrophy of its corresponding
lobes and a compensatory hypertrophy of the remaining liver tissue [ 17 ]. Given that
hepatocytes make up most of the liver volume, this observed atrophy and loss of
volume is mainly caused by apoptosis and necrosis of hepatocytes [ 18 ]. The exact
mechanism of hypertrophy unique to liver regeneration is not completely known.
However, considering the speed of regeneration, a very early trigger—possibly an
abrupt change in a physiological parameter—may be responsible.
Similar to blood flow changes upon portal vein occlusion, one of the most
obvious events in liver regeneration following partial hepatectomy is the sub-
sequent increase in portal blood flow to the remaining lobes. Shear stress resulting
from such increased blood flow on vascular lining could represent a first-line
trigger for liver regeneration after PH. Cell location dictates the specific cells
involved in mechanotransduction of hemodynamic forces in liver vasculature.
2.2 Sensing and Regulation of Blood Flow by the Vasculature
The endothelium is the innermost layer of blood vessels, made up of cells that had
largely been assumed to function primarily as a delivery conduit for oxygen and
nutrients. It has been increasingly appreciated that endothelial cells not only form
vascular networks that deliver nutrients and oxygen throughout the body, but also
establish instructive niches that stimulate organ regeneration through elaboration
of paracrine trophogens. Endothelial cells distributed in different organs exhibit
various morphological and functional attributes. Arteries and veins have distinct
structures, with arteries comprised of three layers (tunica intima, tunica media and
tunica adventitia), while veins consist of only two. The tunica intima is a single
layer of simple squamous endothelium attached to a sub-endothelial connective
tissue layer; the tunica media, mostly present in arteries, contains circularly
arranged elastic fiber, connective tissue, and polysaccharides; the tunica adventitia
is made of connective tissue and nerves. In the case of arteries, the tunica media