Adhesion Molecules in Kidney Diseases - Adhesion Molecules - page 238

INTRODUCTION
In the kidney, the specii c permeability and transport properties of the nephron
segments are determined by the cyto-architecture of the epithelial cells and also
by the cell-cell and cell-matrix interactions which involve specialized junctional
complexes composed of specii c cell adhesion molecules. Disorders in the
functioning of these molecules can af ect renal function.
h e glomerular i ltration process involves the passage of solutes, electrolytes
and low molecular proteins through the porous glomerular endothelium and
through the glomerular basement membrane (GBM). In the i nal step of the
i ltration process they pass through the slit diaphragm that bridges adjacent
foot processes deriving from dif erent podocytes. h e slit diaphragm has been
described as having an hourglass shape with high expression levels of P-cadherin
and α- and β-catenin (Reiser et al. 2000), although some authors have reported
no P-cadherin and α- and β-catenin localization in this site (Yaoita et al. 2002). In
addition, nephrin, an associated protein NEPH1 and the transmembrane protein
Fat1 (a member of the Fat subclass of cadherins) are located in the slit diaphragm
region (Chugh et al. 2003).
h e specii c barrier and permeability characteristics of the tubular segments
of the nephron are determined by the functional state of the apical junctional
complexes. h ese junctional complexes are necessary to restrict permeability,
establish epithelial polarity, and direct the trai c of membrane proteins to either
the apical or the basolateral cell surface, and for the normal transport of solutes
and electrolytes across the tubular barrier (Crean et al. 2004).
h is chapter summarizes the families of adhesion molecules expressed in
normal renal tissue and the changes that occur in the dif erent types of kidney
disease.
Adhesion Molecules in Normal Kidney
h e expression of adhesion molecules in the normal human kidney is summarized
in Table 1.
Claudins
h e apical junctional complex has been considered to consist of two primary units.
Occludin and the claudins are the structural components of the tight junction
(TJ) and are the main determinants of paracellular permeability in the tubular
segments of the nephron (Gonzalez-Mariscal et al. 2003). Occludin and zonula
occludens-1 (ZO), ZO-2 and ZO-3 are integral membrane proteins that interact
with each other and anchor the junctional complex to the cytoskeletal elements
of adjacent cells (Van Itallie et al. 2006). Claudins, but not occludin, are thought
to constitute the backbone of TJ. In the kidney, the claudin expression pattern