Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation?

Abstract

Polycystic kidney disease (PKD) is inherited as a dominant or recessive trait or can be provoked by environmental factors. The disease is characterized by the growth of large epithelial-lined cysts derived from the nephrons and collecting ducts of affected kidneys. Cysts are thought to initiate as small dilations in renal tubules, which then expand into fluid-filled cavities of relatively large size. Cyst formation appears to involve increased cell proliferation, reversal of tubular epithelial polarity, and epithelial fluid secretion. In addition, a number of pronounced extracellular matrix changes have been found in the cystic kidneys of several animal models and in human autosomal dominant PKD. These abnormalities include thickened, laminated basement membrane, increased expression of alpha 1 type IV collagen and laminins B1 and B2, and changes in heparan sulfate proteoglycan and fibronectin. Some of these changes can also be seen in vitro, reflecting intrinsic abnormalities, and may be associated with abnormal tubular morphogenesis early in cyst formation as well as later in cyst expansion. We have been investigating gene expression in the C57BL/6J-cpk mouse, which has an autosomal recessive form of PKD, to determine the genetic basis of the abnormal tubule cell growth and morphology manifested during cyst formation.(ABSTRACT TRUNCATED AT 250 WORDS)