16 research outputs found
The pathogenesis of polycystic kidney disease
Polycystic kidney disease (PKD) is a genetic
or acquired disorder characterized by progressive
distention of multiple tubular segments and manifested
by fluid accumulation, growth of non-neoplastic
epithelial cells and remodeling of the extracellular
matrix resulting ultimately in some degree of renal
functional impairment, with the potential for regression
following removal of the inductive agent(s). It is due
to an aberration of one or more factors regulating
tubular morphogenesis. Human PKD can pursue a
rapid course with renal failure occurring perinatally
(infantile PKD) or an indolent course without renal
failure developing during the life of the individual
(adult PKD). Human acquired PKD develops in atrophic
and scarred end-stage kidneys with non-cystic forms
of renal disease. Cell proliferation, fluid secretion,
impaired cell-cell and cell-matrix interaction, defective
function of the Golgi apparatus, cell undifferentiation,
and an abnormal matrix have been implicated in the
pathogenesis of PKD based on clinical and experimental
studies.
Under normal conditions, the dynamic turnover of
tubular epithelia and matrices are tightly regulated to
maintain tubular morphology. The basic defect in PKD
is tubular dysmorphogenesis. Our finding indicates that
the principal phenotypic features of autosomal dominant
PKD (ADPKD) are altered structure and function of the
Golgi complex, altered structure and composition of the
matrix and cell undifferentiation, al1 of which are
probably interrelated. If the gene product of the ADPKD
1 gene results in a defective matrix, the abnormal Golgi
function and cell differentiation may be due to faulty
matrix-cell communication