Differentiation and cell polarity during renal cyst formation in the Han:SPRD (cy/+) rat, a model for ADPKD.
Despite the recent positional cloning of genes responsible for autosomal dominant polycystic kidney disease (ADPKD), the exact pathogenetic mechanisms underlying this disorder are still unclear. To learn more about cyst formation, we investigated cell differentiation and cell polarity in the Han:SPRD (cy/+) rat between 21 days and 60 wk of age. At early stages of cyst development, alkaline phosphatase, aquaporin-1, NaSi-1 cotransporter, and Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) were expressed normally. Clusterin mRNA was only sparsely expressed at the onset of cystic degeneration and increased thereafter, being highest in noncystic nephron segments. In cyst wall cells, clusterin on the one hand and alkaline phosphatase, aquaporin-1, NaSi-1-cotransporter, and Na(+)-K(+)-ATPase on the other were expressed in a mutually exclusive fashion. No change in cell polarity could be observed at any stage. Our data therefore argue against a change in cell polarity and against an early arrest in normal tubular development during cyst formation in the Han:SPRD (cy/+) rat model of ADPKD but favor the hypothesis that tubular epithelia develop in an orderly fashion and degenerate thereafter.
Obermüller
N
N
Medical Research Center, Klinikum Mannheim, University of Heidelberg, Germany.
Gretz
N
N
Kriz
W
W
van der Woude
F J
FJ
Reilly
R F
RF
Murer
H
H
Biber
J
J
Witzgall
R
R
D000375:Aging / Q000502:physiology*; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D015415:Biomarkers; D002454:Cell Differentiation; D016764:Cell Polarity; D051152:Clusterin; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000096:biosynthesis; D006579:Heterozygote; D017403:In Situ Hybridization; D007473:Ion Channels / Q000096:biosynthesis; D007668:Kidney / Q000254:growth & development / Q000502:physiology*; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018832:Molecular Chaperones; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011922:Rats, Mutant Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D014158:Transcription, Genetic
C496022:Aqp1 protein, rat; D020346:Aquaporins; D015415:Biomarkers; D051152:Clusterin; D006023:Glycoproteins; D007473:Ion Channels; D018832:Molecular Chaperones; D012333:RNA, Messenger; D051398:Aquaporin 1; D000469:Alkaline Phosphatase; D000254:Sodium-Potassium-Exchanging ATPase