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Involvement of P2Y Receptors in TGFβ‐Induced EMT of MDCK Cells
Author(s) -
Wolff Christine Irene,
Bundey Richard A.,
Insel Paul A.
Publication year - 2008
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.22.1_supplement.942.5
Subject(s) - p2y receptor , receptor , epithelial–mesenchymal transition , biology , transforming growth factor , microbiology and biotechnology , kidney , medicine , purinergic receptor , cancer research , endocrinology , chemistry , downregulation and upregulation , gene , biochemistry
Epithelial‐to‐mesenchymal transition (EMT) contributes to renal tubulointerstitial fibrosis, a common pathway leading to end‐stage renal disease. EMT can be induced in certain renal cells by transforming growth factor beta (TGFβ) and results in the phenotypic conversion of tubular epithelia to fibroblasts, reduction of E‐Cadherin expression and induction of α‐smooth muscle actin (αSMA). Since nucleotides can be released during renal injury, we hypothesized that P2Y (nucleotide) receptors contribute to EMT of renal epithelial cells. To test this hypothesis, we used a well‐characterized renal epithelial cell line, Madin Darby Kidney Cells (MDCK), and examined the role of P2Y receptors in TGFβ‐induced EMT. Quantative PCR experiments (used to identify P2Y receptor expression) revealed P2Y2 > P2Y11 > P2Y1 = P2Y14 > P2Y6 = P2Y13 > P2Y12 = P2Y4 as the relative order of abundance. TGFβ treatment reduced the expression of P2Y13 mRNA, elevated P2Y11 and P2Y14 mRNA levels without substantial changes in mRNA expression of P2Y1 and P2Y2. The P2Y agonist ATPγS inhibited protein expression of the EMT marker αSMA in response to TGFβ without influencing the E‐Cadherin decrease or morphological changes. These results indicate that TGFβ‐promoted EMT differentially regulates expression of P2Y receptor subtypes of MDCK cells and that P2Y receptor activation potentially blunts features of the EMT phenotype. Supported by grants from NIH.