Adhesion Molecules in Kidney Diseases - Adhesion Molecules - page 240

Table 2 Expression of major adhesion molecules in renal diseases

Renal diseases Adhesion molecules

Membranous glomerulonephritis VLA-3 , VCAM-1 and PECAM-1 , E-selectin ,

a-integrin

IgA nephropathy ICAM-1 , VCAM-1 , α1β1 and α5β1 integrin

Crescentic glomerulonephritis ICAM-1 , VCAM-1 , α2β1, α3β1, α5β1,

α5β3 integrins

Glomerulosclerosis Integrin α1β1

Renal transplant rejection ICAM-1 , VCAM-1 , β6 integrin ,

VE-cadherin

Up- or down-regulations of adhesion molecules are expressed by the symbol or , respectively.

and -10b to specii c nephron segments, while their mRNAs are preferentially
expressed in either the medulla or cortex, respectively (Table 1) .

Integrins

Integrins are heterodimeric transmembrane proteins made up of an α and β
subunit. h ey are ubiquitously distributed and mediate diverse biological functions,
including cell-cell and cell-matrix interactions, cell polarity, cell migration and
angiogenesis. h ey serve as receptors for a number of morphogenetic extracellular
matrix (ECM) proteins, including laminins, collagens, i bronectin, osteopontin,
nephronectin, vitronectin and tenascin. Podocytes predominantly express the
α3 integrin subunit, proximal tubules express the α6 subunit, and distal tubules
express α2, α3 and α6 subunits.
h e β1 integrins have been identii ed on the cell membranes of lymphocytes
and glomerular, endothelial, epithelial and mesangial cells. β1 integrins are
also referred to as the VLA family. h e β1 integrin VLA-4 (α4β1) is expressed
by lymphocytes, basophils and eosinophils, and binds to vascular cell adhesion
molecule 1 (VCAM-1). Epithelial and mesangial cells express VCAM-1, facilitating
the interaction of these cells with leukocytes bearing VLA-4.
h e β2 integrins include several CD11/CD18 subtypes expressed exclusively on
leukocytes.
CD11a/CD18 (LFA-1) binds primarily to the inducible receptor intercellular
adhesion molecule 1 (ICAM-1) on endothelial cells, epithelial cells, glomerular
mesangial cells and leukocytes. CD11a/CD18 also binds to the receptor ICAM-2
on endothelial cells, as well as to ICAM-3 on leukocytes. CD11b/CD18 also binds
ICAM-1 and, in addition, engages the complement fragment C3b, factor X and
i brinogen.
h e β3 integrin subfamily includes the platelet receptor GPIIb/IIIa (CD41/
CD61), which binds i brinogen and Willebrand's factor. h is integrin is a potential
target for modulating platelet-mediated kidney diseases.