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Abstract: PO1242

Loss of Polycystin Function in Lymphatic Cells Impair CTP1a Expression and Fatty Acid Uptake

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Basquin, Denis, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Liang, Jinqing, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Watnick, Terry J., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Outeda, Patricia, University of Maryland School of Medicine, Baltimore, Maryland, United States

Homozygous Pkd1 or Pkd2 null mutant mice die at mid-gestation due to vascular abnormalities including edema and hemorrhage. We have previously shown that edema in Pkd1 and Pkd2 knock out mice is due to abnormal lymphatic morphogenesis, with grossly dilated, blood filled dermal lymphatic vessels. Because proper lymphatic development is supported by fatty acid β-oxidation (FAO), we probed fatty acid transport in PC1/PC2 lymphatic endothelial cells (LECs).


Pkd1 and Pkd2 mutant LECs were isolated from mouse E14.5 embryos or generated using lentiviral shRNAs against PKD1 or PKD2 in human dermal LECs (HDLECs). Protein levels of PC1, PC2 and CPT1a were determined by western blotting and CPT1a/CPT2 mRNA levels were analyzed by qRT-PCR. Fatty acid uptake was assessed by BODIPY® 558/568 C12 staining of control and Pkd mutant LECs pre-incubated with or without 50 μM palmitate, and counterstained with mitotracker. Cells were imaged by confocal microscopy and the relative abundance of lipid droplets were quantified using ImageJ software. Each experiment was repeated 3 times and pairs of means (mutant versus control) were compared using Student’s T-test.


Embryonic Pkd1-/- and Pkd2-/- murine LECs exhibit a robust decrease of CPT1a protein levels. In addition, CPT1a protein levels were significantly reduced in PKD1 and PKD2 depleted HDLEC, suggesting a conserved role of Pkd1/2 in CPT1a regulation. PC1 and PC2 depletion in HDLECs results in an accumulation of cytoplasmic lipid droplets which often colocalized with mitochondria, indicative of impaired fatty acid utilization. The ability of PKD mutant cells to metabolize fatty acids is further challenged by pre-treatement with 50μM palmitate, which exacerbates the accumulation of lipid droplets.


Our results highly suggest that polycystin function is required to maintain normal levels of CPT1a expression and fatty acid transport to mitochondria in LECs. We thus speculate that a defect in FAO with consequent dysregulation of gene expression is the basis of impaired
lymphangiogenesis in Pkd1/2 mutant embryos.


  • NIDDK Support