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Abstract: TH-PO980

Serotonin Receptor Expression in the Normal Adult Human Kidney and in Glomerular Diseases

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Authors

  • van Roeyen, Claudia R.C., RWTH University of Aachen, Aachen, Germany
  • Vu, Jenny, RWTH University of Aachen, Aachen, Germany
  • Smeets, Bart, Radboud University Medical Center, Nijmegen, Netherlands
  • Moeller, Marcus J., RWTH University of Aachen, Aachen, Germany
  • Maroteaux, Luc, INSERM U839, Paris, France
  • Groene, Hermann-Josef, German Cancer Research Center, Heidelberg, Germany
  • Floege, Jürgen, RWTH University of Aachen, Aachen, Germany
  • Ostendorf, Tammo, RWTH University of Aachen, Aachen, Germany
  • Braun, Gerald S., RWTH University of Aachen, Aachen, Germany
Background

Serotonin (5-HT) is the phylogenetically oldest neurotransmitter and acts via specific receptors. Serotonin receptors 5-HT2A and 5-HT2B are G-protein-coupled and mediate vasoconstriction and hypertension. The 5-HT2A receptor is also engaged in blood coagulation and wound healing. Little is known about the function of 5-HT and its receptors 5-HT2A and 5-HT2B in the normal kidney or during renal disease.

Methods

Localization of 5-HT2A and 5-HT2B receptors was analysed by immunohistochemistry in the human healthy kidney and during renal disease. Serum 5-HT and urine 5-HT metabolite 5-HIAA concentrations were measured by HPLC. In vitro studies were performed to identify the role of 5-HT2A and 5-HT2B receptors in primary murine glomerular parietal epithelial cells (PECs). Mice with 5-HT2A and 5-HT2B deletions are available.

Results

In the normal human kidney (living donor biopsies), 5-HT2A and 5-HT2B receptors localized to PECs, proximal tubuli and the loop of Henle. In all renal diseases investigated, 5-HT2A- and 5-HT2B-expression in tubuli was maintained. In glomeruli, the number of 5-HT2B-positive cells increased significantly with disease. Serum 5-HT concentrations were significantly reduced in patients with rapidly progressive glomerulonephritis (RPGN), whereas 5-HT metabolite concentrations in tendency increased in the urine of these patients. By immunofluorescence, glomerular 5-HT2B-positive cells could be identified as PECs. In biopsies of patients with IgA nephropathy or RPGN, the cell diameter of 5-HT2B-positive PECs was significantly increased in comparison to receptor-negative PECs. In primary PECs in vitro, removal of serotonin from culture medium reduced the expression of activation markers. Vice versa, activation of 5-HT2A and 5-HT2B receptors induced an overexpression of CXCR4 and VCAM.

Conclusion

In summary, we demonstrate for the first time the constitutive expression of 5-HT2A and 5-HT2B receptors in the adult human kidney with glomerular upregulation in different renal diseases. Our studies identify PECs as the primarily cell type involved in serotonin receptor upregulation in glomerular disease. Further in vivo studies in murine models of glomerular disease are currently under way in order to elucidate the potential pathophysiological role of these receptors.

Funding

  • Government Support - Non-U.S.