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Different signaling mechanisms are involved in vasopressin‐induced proliferation of orpk cilia (+) and orpk cilia (−) renal cells derived from a mouse model of polycystic kidney disease
Author(s) -
Garnovskaya Maria N,
Bunni Marlene A,
Bell P. Darwin,
Raymond John R,
Coaxum Sonya D
Publication year - 2011
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.25.1_supplement.lb503
Subject(s) - vasopressin , mapk/erk pathway , cilium , microbiology and biotechnology , endocrinology , medicine , cell growth , polycystic kidney disease , signal transduction , biology , extracellular , chemistry , kidney , biochemistry
Arginine vasopressin (AVP) is a powerful modulator of cystogenesis in polycystic kidney disease (PKD). We studied signaling pathways activated by AVP in the orpk cilia (−) collecting duct cell line, derived from a mouse model of PKD, and in the control, orpk cilia (+) cell line. We measured changes in extracellular pH as a reflection of Na + /H + exchange (NHE) activity with a Cytosensor microphysiometer, assessed extracellular signal regulated kinase (ERK) activation by Western blotting, cAMP production by immunoassay, and cell proliferation by a bromodeoxyuridine uptake. AVP stimulated cAMP production, supporting the expression of functional AVP receptors in both cell lines. However, exposure to AVP caused ≥20% increases in NHE activity in control cells but only minor (~10%) increases in orpk cilia (−) cells. Similarly, AVP stimulated ERK phosphorylation ≥80% only in control cells. Exposure to 1 μM AVP resulted in ≥25% increase in proliferation of control cells, and an ERK inhibitor (PD98059) blocked this effect suggesting a critical role for ERK in AVP mitogenic activity. AVP‐induced cell proliferation in orpk cilia (−) cells was more pronounced (~45% increase), and was not sensitive to ERK inhibition. In summary, AVP induces different pathways to stimulate proliferation in orpk cilia (+) and orpk cilia (−) cells. These studies are important because of the proposed role of AVP in the pathogenesis of PKD.