Regulation of the human PDZK1 expression by peroxisome proliferator-activated receptor alpha.

Although PDZK1 is a well-known adaptor protein, the mechanisms for its role in transcriptional regulation are largely unknown. The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. Previously, we established a tetracycline-regulated human cell line that can be induced to express PPARalpha and identified candidate target genes, one of which was PDZK1. In this study, we cloned and characterized the promoter region of the human pdzk1 gene and determined the PPAR response element. Finally, we demonstrate that endogenous PPARalpha regulates PDZK1 expression.

Analysis of PPAR alpha function in human kidney cell line using siRNA.

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPARalpha is mainly expressed in the liver, kidney, heart and muscle. PPARalpha activates fatty acid catabolism, stimulates gluconeogenesis and ketone body synthesis and is involved in the control of lipoprotein assembly. Although PPARalpha is well characterized in the liver, its physiological function is unknown in the kidney. To investigate the intimate function of PPARalpha in the kidney, we analyzed the target gene expression in human metastatic renal cell carcinoma cell line, Caki-1, using small interfering RNA (siRNA) against PPARalpha and real-time RT-PCR methods. We found that some selected genes (long-chain fatty-acid-CoA ligase (FACL1), carnitine palmitoyltransferase 1A (CPT1A), adipose differentiation-related protein (ADRP) and aquaporin 3 (AQP3)) were down-regulated by PPARalpha siRNA. These results suggest that PPARalpha regulates fatty acid metabolism and body water homeostasis in this cell line.