Biomedical Engineering Reference
In-Depth Information
kidney disease (ADPKD) is due to germ-line and somatic PKD1 or PKD2 gene
mutations. h e majority of ADPKD cases are caused by mutations in the PKD1
gene, which codes for polycystin-1. Huan
et al.
(1999) showed that polycystin-1
co-localized with the cell adhesion molecules E-cadherin and α-, β-, and γ-catenin
and co-precipitated and co-migrated with them on sucrose density gradients. h ey
concluded that polycystin-1 is in a complex containing E-cadherin and α-, β-, and
γ-catenin. h ese observations raise the question of whether the defects in cell
proliferation and cell polarity observed in ADPKD are mediated by E-cadherin or
the catenins (Huan
et al.
1999). Analysis of cDNA array identii ed an aberrant β4
integrin expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main α6β4
integrin ligand, was also abnormally expressed in ADPKD. Studies performed with
ADPKD cyst-lining epithelial cells indicate that integrin α6β4-Ln-5 interactions
are involved in cellular events of potential importance for cystogenesis. h ese
studies highlight the role of Ln-5 and α6β4 integrin in the adhesive and motility
properties of cyst-lining epithelial cells and further suggest that integrins and ECM
modii cations may be of general relevance to kidney epithelial cell cyst formation
and cyst enlargement in ADPKD (Joly
et al.
2003).
Renal Transplant Rejection
Renal transplant rejection is a complex continuum of immunological and non-
immunological processes that result in grat dysfunction and eventual loss. h e
cellular and molecular events lead to a group of well-characterized pathological and
clinical patterns of rejection. Cells of the immune system ini ltrate the grat from
nearby lymphoid organs and the bloodstream by a multi-step process. h ey roll
along the vessel wall through interactions between selectins on the endothelium
and receptors on immune cells and adhere to the vessel endothelium following
chemokine release. Adhesion molecules and chemokines are important rejection
regulators and appear to be targets for immunotherapy. Adhesion molecules on T
cells include LFA-1, which interacts with ICAM-1 and -2; CD2, which interacts
with CD58 (LFA-3); and VLA-4 (a4, b1 integrin CDw49d, CD29), which interacts
with VCAM-1, CD106.
Grat rejection is accompanied by a de novo expression of ICAM-1 on the
renal tubular cells which, however, is not specii c to rejection. Increased ICAM-1
expression on the renal vascular endothelium has occasionally been described and
signii cant de novo ICAM-1 expression on tubules supports the contact between
tubular cells and ini ltrating leukocytes. In acute rejection, de novo VCAM-1
expression is induced on the renal vascular endothelium and is upregulated in
the tubules. VCAM-1 plays a pathogenic role in rejection by potentiating the
interaction between tubular cells and ef ector cells and by promoting leukocyte
migration into the renal tissue. Upregulation of β6 integrin, which is indispensable
for the activation of TGF-β1, has been investigated in chronic renal allograt
dysfunction. TGF-β1 and -β6 integrin reactivity were observed in the distal
