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Regulation of 24p3 Receptor (24p3R/SLC22A17) Expression by Tonicity in Rodent Renal Inner Medullary Collecting Duct (IMCD) Cells
Author(s) -
Thevenod Frank,
Langelueddecke Christian,
Probst Stephanie,
Scharner Bettina,
Betten Richard,
Mese Kemal,
Edemir Bayram
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.741.2
Subject(s) - osmotic concentration , microbiology and biotechnology , renal medulla , biology , tonicity , cell growth , receptor , flow cytometry , cyclin d1 , chemistry , cell , cell cycle , kidney , endocrinology , biochemistry
Background and Aims The 24p3/NGAL/lipocalin‐2 receptor (24p3R/SLC22A17) is apically expressed in rodent collecting ducts, including IMCD, where it may mediate protein endocytosis (Langelueddecke C. et al. J. Biol. Chem. 287 :159–169, 2012) and induce pro‐inflammatory and pro‐fibrotic signalling in response to albuminuria (Dizin E. et al. Am. J. Physiol. Renal Physiol. 305 :F1053‐F1063, 2013). Cells of the inner medulla are exposed in vivo to a hyperosmotic environment, which requires an adaptive response for survival. Interestingly, we have identified a putative TonEBP DNA consensus motif in the 24p3R promoter sequence. Here we investigated the expression of 24p3R in cultured IMCD cells that were exposed to increased osmolarity. Methods Cultured mouse IMCD cells (mIMCD3) and rat primary IMCD cells were cultured in 300 – 900 mOsm/kg for 1–6 days. Hypertonicity was induced by equimolar addition of NaCl + urea. 24p3R expression and localization were determined by qPCR, immunoblotting, surface biotinylation, flow cytometry and immunofluorescence microscopy. Results Hypertonicity decreased cell proliferation and was accompanied by suppression of the cell proliferation genes c‐myc and cyclin‐D1 in mIMCD3 cells, which may reflect cellular stress and damage. Hypertonicity increased 24p3R mRNA and 24p3R protein expression and localization in plasma membranes of mIMCD3 and primary IMCD cells. Furthermore, plasma membrane localization of 24p3R was associated with increased dimerization of the protein. Conclusions Hyperosmotic environment decreases proliferation of IMCD cells but increases plasma membrane expression and dimerization of 24p3R, which may be mediated by TonEBP and contribute to adaptation of IMCD cells to osmotic stress. Support or Funding Information Funded by DFG TH345/11‐1 and ZBAF