title: Increased activity of activator protein-1 transcription factor components ATF2, c-Jun, and c-Fos in human and mouse autosomal dominant polycystic kidney disease.
abstract: 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.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ngoc Hang
authors.initials: NH
authors.lastname: Le
authors.forename: Annemieke
authors.initials: A
authors.lastname: van der Wal
authors.forename: Paola
authors.initials: P
authors.lastname: van der Bent
authors.forename: Irma S
authors.initials: IS
authors.lastname: Lantinga-van Leeuwen
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Hans
authors.initials: H
authors.lastname: van Dam
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1