Biomedical Engineering Reference
In-Depth Information
24.2.2
Epithelial Polarity, Differentiation, and Function
The cell surface attaching to the basement membrane is called
the basal surface. The opposite side facing the external environ-
ment, or the lumen, is called the apical (free) surface. This cellu-
lar environment generates apical-basal polarity. In all epithelial tis-
sues, the apical domain is separated from the basolateral region by
tight junctions. Epithelial polarity is initiated by cell-cell and cell-
matrix interactions
26
and reinforced and maintained by polarized
distributionofproteinsandlipids.
27
Moleculesthatestablishepithe-
lial polarity include Cdc42, PAK1, PI3K, PTEN, Rac, and the PAR
proteins.
28
A normal apical-basal polarity is essential for epithelial
cells to perform diverse functions. The simple columnar epithelium
of the mammalian intestine and kidney is the most studied polar-
ized tissue. It is made up of interconnected tubular networks. In
contrast, the liver consists of interconnected single-layer cell sheets
of hepatocytes. The hepatocytes' plasma membrane is divided into
three domains: the basal (sinusoidal) domain, the site for trans-
membraneproteinsthatrecognizesspecificmatrixcomponentsand
is responsible for exchanging metabolites with blood; the lateral
domain, the site for cell-cell adhesion via intermediate junctions
and desmosomes and intercellular communication via gap junc-
tions;andtheapical(bilecanalicular)domain,thesurfaceofhepato-
cytes for secreting bile acid and detoxification products.
29
,
30
These
microscale bile canaliculus assemble into 3D interconnected chan-
nelsin liver tissue.
To obtain functional cells in epithelial tissue engineering, it is
important to establish and maintain proper membrane polarity.
Renal tubular cells have been used as a model in the study of
epithelial polarity. To mimic the
in vivo
epithelial tissue structure,
the formation of cysts in 3D culture systems has been investi-
gated. Wang
et al.
found that cell-cell and cell-substratum contact
has a distinct role in the development of renal epithelial polarity.
31
RecentstudiesfurtherdemonstratedthatE-cadherin-mediatedcell-
celladhesiontriggeredrenalcellpolarity.
32
ECMproteinsalsoaffect
the formation of epithelial polarity.
β
1-integrin-mediated Rac1
activation leads to laminin assembly, which in turn orients epithe-
lial apical polarity.
33
,
34
Madin-Darby canine kidney (MDCK) renal
tubular cells grown on top of type I collagen gel lost their polarity
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