Genetically based
polycystic kidney diseases include autosomal dominant (
ADPKD) and recessive (
ARPKD)
polycystic kidney diseases, nephronophthisis and medullary cystic disease. The PKD1 and PKD2 genes responsible for
ADPKD and their respective encoded
proteins polycystin-1 and polycystin-2 are under intense study and clues are developing as to their function and roles in the disease process. Structure-function analysis suggests that
polycystins form
multiprotein complexes with focal adhesion and cell-cell adherens junction
proteins, which then initiate intracellular signaling events culminating in regulation of transcription of genes controlling proliferation and differentiation. Although less is known about the PKHD-encoded fibrocystin responsible for
ARPKD or about the NPH1-encoded nephrocystin responsible for nephronophthisis, it is proposed that they function in the same cellular pathway involving
protein-
protein interactions, signal transduction and regulation of gene transcription.
ADPKD epithelia are more adherent to
collagen, less migratory, fail to recruit FAK to
polycystin complexes and show aberrant, persistent expression of the fetal genes Erb-B2 and beta2 subunit of NaK-
ATPase after birth. It is suggested that the function of the
polycystin complex is to act as a key developmental regulator of renal tubule morphogenesis.