Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney.

Abstract

Polycystic kidney disease 1 (PKDI) is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease. We have studied PKDI mRNA, with an RNase protection assay, and found widespread expression in adult tissue, with high levels in brain and moderate signal in kidney. Expression of the PKD1 protein, polycystin, was assessed in kidney using monoclonal antibodies to a recombinant protein containing the C terminus of the molecule. In fetal and adult kidney, staining is restricted to epithelial cells. Expression in the developing nephron is most prominent in mature tubules, with lesser staining in Bowman's capsule and the proximal ureteric bud. In the nephrogenic zone, detectable signal was observed in comma-and S-shaped bodies as well as the distal branches of the ureteric bud. By contrast, uninduced mesenchyme and glomerular tufts showed no staining. In later fetal (>20 weeks) and adult kidney, strong staining persists in cortical tubules with moderate staining detected in the loops of Henle and collecting ducts. These results suggest that polycystin's major role is in the maintenance of renal epithelial differentiation and organization from early fetal life. Interestingly, polycystin expression, monitored at the mRNA level and by immunohistochemistry, appears higher in cystic epithelia, indicating that the disease does not result from complete loss of the protein.

Coordinate Expression of the Autosomal Dominant Polycystic Kidney Disease Proteins, Polycystin-2 And Polycystin-1, in Normal and Cystic Tissue

“…11 The renal phenotypes are also similar, although PKD2 patients have milder disease and a lower incidence of hypertension. 10,12 Consistent with the sug-gestion that ADPKD proteins have related functions and similar systemic disease phenotypes, expression of PKD1 13 and PKD2 4 has been found in most human tissues. To date, however, the different cell types expressing these proteins have not been systematically defined.…”

“…The production and characterization of two polycystin-1 mAbs, PKS-A and 7e12, has been described previously 13,21 . The epitope detected by PKS-A is contained within the final 233 aa of the C-terminus of polycystin-1, whereas 7e12 was raised to an epitope in the N-terminal region (flank-LRR-flank domain) of polycystin-1.…”

“…Evidence of loss of heterozygosity in individual PKD1 renal 16,17 and liver cysts 18 and recent data from targeted disruption of the mouse Pkd2 gene 19 favor a two-hit mechanism involving somatic inactivation of the normal allele. However, studies of PKD1 cystic tissue have shown polycystin-1 expression 13,20,21 . No corresponding studies of human PKD2 tissue have yet been described.…”

“…To understand the cellular basis for the renal and extrarenal manifestations of ADPKD, we examined the expression of polycystin-2 and polycystin-1 in human fetal tissues at different ages of gestation, using antisera raised to an epitope in the predicted C-terminal region of PKD2 and two previously described polycystin-1 mAbs 13,21 . The expression of polycystin-2 was also examined in PKD2 cystic kidney and liver tissue for clues to the mutational basis of cyst formation.…”

Aldosterone as a renal growth factor

“…Susceptible individuals have a genetic predisposition to developing autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) through mutations in the genes encoding the fibrocystin or polycystin 1 and 2 genes respectively [29,30]. The products of these genes are multi-functional structural membrane proteins that have roles in cell polarization, tight junction integrity, ion transport and signal transduction.…”