Regulation of PDZ domain containing 1 (PDZK1) Expression by Hepatocyte Nuclear Factor 1 alpha (HNF1α) in Human Kidney

Prestin, Katharina and Hussner, Janine and Ferreira, Celio and Seibert, Isabell and Breitung, Vivien and Zimmermann, Uwe and Meyer Zu Schwabedissen, Henriette Elisabeth. (2017) Regulation of PDZ domain containing 1 (PDZK1) Expression by Hepatocyte Nuclear Factor 1 alpha (HNF1α) in Human Kidney. American Journal of Physiology - Renal Physiology, 313 (4). F973-F983.

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Official URL: http://edoc.unibas.ch/55969/

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In the renal proximal tubule the secretion and reabsorption of glomerularly filtrated compounds is realized by a functional network of uptake and efflux transporters. The activity and localization of several transporters expressed at the apical tubular membrane is regulated by the membrane associated protein PDZ domain containing 1 (PDZK1). We aimed to characterize the transcriptional regulation of this modulator of renal transport. Coexpression analyses of PDZK1 and putative regulators were performed using human kidney samples. Protein and mRNA expression of PDZK1 in renal proximal tubule epithelial cells after adenoviral transfer and siRNA knockdown of transcription factor hepatocyte nuclear factor 1 alpha (HNF1α) was assessed by quantitative real-time PCR and Western blot analysis. Transactivation of the PDZK1 promoter was quantified in cell-based reporter gene assays. Subsequently, the binding of HNF1α to the PDZK1 promoter was verified by in silico analyses and chromatin immunoprecipitation assay. HNF1α positively regulated the promoter activity of PDZK1. Adenoviral overexpression of HNF1α in renal proximal tubule epithelial cells (RPTEC) increased PDZK1 mRNA and protein expression, whereas siRNA knockdown of HNF1α resulted in decreased expression of PDZK1. Our results show that HNF1α, which has previously been described as a modulator of several transporters of the renal transportosome, is also a key determinant of PDZK1 transcription.
Faculties and Departments:05 Faculty of Science
UniBasel Contributors:Hussner, Janine and Meyer zu Schwabedissen, Henriette and Seibert, Isabell
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:15 Aug 2019 10:18
Deposited On:16 Oct 2017 09:43

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