RT Journal Article
SR Electronic
T1 Increased Activity of Activator Protein-1 Transcription Factor Components ATF2, c-Jun, and c-Fos in Human and Mouse Autosomal Dominant Polycystic Kidney Disease
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 2724
OP 2731
DO 10.1681/ASN.2004110913
VO 16
IS 9
A1 Hang Le, Ngoc
A1 van der Wal, Annemieke
A1 van der Bent, Paola
A1 Lantinga-van Leeuwen, Irma S.
A1 Breuning, Martijn H.
A1 van Dam, Hans
A1 de Heer, Emile
A1 Peters, Dorien J.M.
YR 2005
UL http://jasn.asnjournals.org/content/16/9/2724.abstract
AB Autosomal dominant polycystic kidney disease is a common inherited disorder that predominantly manifests with the formation of fluid-filled cysts in both kidneys. The disease can be accounted for by a mutation in either the PKD1 or the PKD2 gene. It was demonstrated previously that aberrant expression of the PKD1 gene product, polycystin-1, results in modification of activator protein-1 (AP-1) transcription factor activity in cultured renal epithelial cells. Here, it is reported that activity of the AP-1 components c-Jun, ATF2, and c-Fos is altered in renal cystic tissue of patients with autosomal dominant polycystic kidney disease and of hypomorphic Pkd1 mice with polycystic kidney disease. Data were obtained using immunohistochemical and Western blot analysis. Significant upregulation of Thr71- and Thr69/71-phosphorylated ATF2 and Ser73-phosphorylated c-Jun and increased c-Fos were detected in small cysts and (dilated) ducts and tubules surrounded by fibrotic interstitium. The data indicate that various AP-1 components are constitutively activated in polycystic kidney disease and suggest that aberrant AP-1 activity is relevant for cyst formation.