Tankyrase-mediated β-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells

Hyun Jun Jung, Sang Yeob Kim, Hyo Jung Choi, Eui Jung Park, Jung Suk Lim, Jørgen Frøkiaer, Søren Nielsen, Tae Hwan Kwon

Research output: Contribution to journalArticle

Abstract

Aquaporin-2 (AQP2) mediates arginine vasopressin (AVP)-induced water reabsorption in the kidney collecting duct. AVP regulates AQP2 expression primarily via Gsα/cAMP/PKA signaling. Tankyrase, a member of the poly(ADP-ribose) polymerase family, is known to mediate Wnt/β-catenin signaling-induced gene expression. We examined whether tankyrase plays a role in AVP-induced AQP2 regulation via ADP-ribosylation of G protein-α (Gα) and/or β-catenin-mediated transcription of AQP2. RT-PCR and immunoblotting analysis revealed the mRNA and protein expression of tankyrase in mouse kidney and mouse collecting duct mpkCCDc14 cells. dDAVP-induced AQP2 upregulation was attenuated in mpkCCDc14 cells under the tankyrase inhibition by XAV939 treatment or small interfering (si) RNA knockdown. Fluorescence resonance energy transfer image analysis, however, revealed that XAV939 treatment did not affect dDAVP- or forskolin-induced PKA activation. Inhibition of tankyrase decreased dDAVP-induced phosphorylation of β-catenin (S552) and nuclear translocation of phospho-β-catenin. siRNA-mediated knockdown of β-catenin decreased forskolin-induced AQP2 transcription and dDAVP-induced AQP2 expression. Moreover, inhibition of phosphoinositide 3-kinase/Akt, which was associated with decreased nuclear translocation of β-catenin, diminished dDAVP-induced AQP2 upregulation, further indicating that β-catenin mediates AQP2 expression. Taken together, tankyrase plays a role in AVP-induced AQP2 regulation, which is likely via β-catenin-mediated transcription of AQP2, but not ADP-ribosylation of Gα. The results provide novel insights into vasopressin-mediated urine concentration and homeostasis of body water metabolism.

Original languageEnglish (US)
Pages (from-to)F473-F486
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Tankyrases
Collecting Kidney Tubules
Aquaporin 2
Catenins
Vasopressins
Arginine Vasopressin
Colforsin
Adenosine Diphosphate
Small Interfering RNA
Up-Regulation
Fluorescence Resonance Energy Transfer
1-Phosphatidylinositol 4-Kinase
Poly(ADP-ribose) Polymerases
Body Water
GTP-Binding Proteins
Immunoblotting

Keywords

  • Aquaporin-2
  • Collecting duct
  • Tankyrase
  • Vasopressin
  • β-catenin

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Tankyrase-mediated β-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells. / Jung, Hyun Jun; Kim, Sang Yeob; Choi, Hyo Jung; Park, Eui Jung; Lim, Jung Suk; Frøkiaer, Jørgen; Nielsen, Søren; Kwon, Tae Hwan.

In: American Journal of Physiology - Renal Physiology, Vol. 308, No. 5, 01.01.2015, p. F473-F486.

Research output: Contribution to journalArticle

Jung, Hyun Jun ; Kim, Sang Yeob ; Choi, Hyo Jung ; Park, Eui Jung ; Lim, Jung Suk ; Frøkiaer, Jørgen ; Nielsen, Søren ; Kwon, Tae Hwan. / Tankyrase-mediated β-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells. In: American Journal of Physiology - Renal Physiology. 2015 ; Vol. 308, No. 5. pp. F473-F486.
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AU - Kim, Sang Yeob

AU - Choi, Hyo Jung

AU - Park, Eui Jung

AU - Lim, Jung Suk

AU - Frøkiaer, Jørgen

AU - Nielsen, Søren

AU - Kwon, Tae Hwan

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AB - Aquaporin-2 (AQP2) mediates arginine vasopressin (AVP)-induced water reabsorption in the kidney collecting duct. AVP regulates AQP2 expression primarily via Gsα/cAMP/PKA signaling. Tankyrase, a member of the poly(ADP-ribose) polymerase family, is known to mediate Wnt/β-catenin signaling-induced gene expression. We examined whether tankyrase plays a role in AVP-induced AQP2 regulation via ADP-ribosylation of G protein-α (Gα) and/or β-catenin-mediated transcription of AQP2. RT-PCR and immunoblotting analysis revealed the mRNA and protein expression of tankyrase in mouse kidney and mouse collecting duct mpkCCDc14 cells. dDAVP-induced AQP2 upregulation was attenuated in mpkCCDc14 cells under the tankyrase inhibition by XAV939 treatment or small interfering (si) RNA knockdown. Fluorescence resonance energy transfer image analysis, however, revealed that XAV939 treatment did not affect dDAVP- or forskolin-induced PKA activation. Inhibition of tankyrase decreased dDAVP-induced phosphorylation of β-catenin (S552) and nuclear translocation of phospho-β-catenin. siRNA-mediated knockdown of β-catenin decreased forskolin-induced AQP2 transcription and dDAVP-induced AQP2 expression. Moreover, inhibition of phosphoinositide 3-kinase/Akt, which was associated with decreased nuclear translocation of β-catenin, diminished dDAVP-induced AQP2 upregulation, further indicating that β-catenin mediates AQP2 expression. Taken together, tankyrase plays a role in AVP-induced AQP2 regulation, which is likely via β-catenin-mediated transcription of AQP2, but not ADP-ribosylation of Gα. The results provide novel insights into vasopressin-mediated urine concentration and homeostasis of body water metabolism.

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