The role of scavenger receptor BI in hepatitis - eTheses Repository ...
The role of scavenger receptor BI in hepatitis - eTheses Repository ...
The role of scavenger receptor BI in hepatitis - eTheses Repository ...
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31<br />
blood bra<strong>in</strong> barrier is permeable only to relatively small molecules such as<br />
sugars. This is achieved by tissue polarisation; the cells found with<strong>in</strong> tissue<br />
layers have dist<strong>in</strong>ct ‘top’ and ‘bottom’ surfaces, termed apical and basolateral<br />
respectively. Each surface will have a specific prote<strong>in</strong> expression pr<strong>of</strong>ile suited<br />
to the tasks it performs. <strong>The</strong> ma<strong>in</strong>tenance <strong>of</strong> tissue <strong>in</strong>tegrity and polarity is<br />
largely mediated by tight junctions. <strong>The</strong>se are lateral structures that form at<br />
cell junctions, b<strong>in</strong>d<strong>in</strong>g adjacent cell membranes together <strong>in</strong> a way that<br />
prevents the free movement <strong>of</strong> solutes across the tissue layer. Tight junctions<br />
are comprised <strong>of</strong> transmembrane prote<strong>in</strong>s such as occlud<strong>in</strong>s, claud<strong>in</strong>s,<br />
junctional adhesion molecules and e-cadher<strong>in</strong>, these <strong>in</strong>teract with the cell<br />
<strong>in</strong>terior via cytoplasmic partners, for <strong>in</strong>stance ZO-1 and c<strong>in</strong>gul<strong>in</strong> (27, 160).<br />
Other types <strong>of</strong> cell junctions <strong>in</strong>clude, gap and adherence junctions which<br />
mediate selective solute exchange and the attachment <strong>of</strong> adjacent cells,<br />
respectively (74).<br />
<strong>The</strong>re are 24 members <strong>of</strong> the claud<strong>in</strong> family and they share a basic structure<br />
with tetraspan<strong>in</strong>s; 4 transmembrane doma<strong>in</strong>s anchor<strong>in</strong>g 2 extracellular (EC)<br />
loops. <strong>The</strong> larger <strong>of</strong> the loops, EC1, is responsible for seal<strong>in</strong>g the tight<br />
junctions and the formation <strong>of</strong> selective ion channels, whereas the other<br />
mediates lateral and oppositional organisation <strong>of</strong> the prote<strong>in</strong> (160).<br />
Intracellular doma<strong>in</strong>s <strong>in</strong>teract with adaptor molecules that tether the prote<strong>in</strong>s<br />
to the cytoskeleton (160). <strong>The</strong> liver is a composed <strong>of</strong> highly polarised units<br />
called lobules and claud<strong>in</strong>-1 (CLDN1) is expressed <strong>in</strong> the tight junctions<br />
between hepatocytes that ma<strong>in</strong>ta<strong>in</strong> these structures (157, 160).