Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway

Ando, Fumiaki; Sohara, Eisei; Morimoto, Takeshi; Yui, Naofumi; Nomura, Naohiro; Kikuchi, Eriko; Takahashi, Daichi; Mori, Takayasu; Vandewalle, Alain; Rai, Tatemitsu; Sasaki, Sei; Kondo, Yoshiaki; Uchida, Shinichi

doi:10.1038/ncomms13636

Cited by 56 publications

(55 citation statements)

References 59 publications

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“…Because the amount of phosphorylated AQP2 at S269 is well-correlated with apical AQP2 expression in renal collecting ducts 7 , 31 , 32 , the distribution of AQP2 in mpkCCD cells was examined by immunofluorescent staining. Z-stack and apical surface images demonstrated that Ht31, but not Ht31P, significantly increased apical AQP2 expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The mpkCCD cells were washed twice with phosphate-buffered saline (PBS) and then solubilized in 200 µL of lysis buffer as previously described 32 . For analysis of the cell fractions, the mpkCCD cells were incubated with 650 µL of 1% Triton X-100 in PBS for 3 min before cell lysis, yielding a detergent-soluble cytosol fraction and an insoluble membrane fraction 29 .…”

Section: Methodsmentioning

confidence: 99%

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AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

et al. 2018

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Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells. In vivo, the low molecular weight compound 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute a promising lead compound for the treatment of congenital NDI caused by V2R mutations.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

et al. 2018

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“…Therefore, we focused on the classic calcium signal transducer Wnt5a, which is a ligand of frizzled (Fzd) receptors [ 27 – 30 ], and found that the Wnt5a/calcium/calmodulin/calcineurin signaling pathway induced phosphorylation, trafficking, and mRNA expression of AQP2 (Fig. 2 ) [ 31 ]. W7 and CyA were found to totally inhibit Wnt5a-induced AQP2 activation.…”

Section: Activators Of Calcium Signalingmentioning

confidence: 99%

“…W7 and CyA were found to totally inhibit Wnt5a-induced AQP2 activation. These effects of Wnt5a on AQP2 were examined using mpkCCD Cl4 cells, which are one of the most frequently used cell lines for the reliable analysis of AQP2 and exhibit endogenous expression of V2R and AQP2 [ 31 – 42 ]. Remarkably, contrary to the results of isolated perfused IMCD, W7 and CyA did not inhibit the effects of vasopressin on AQP2 phosphorylation in mpkCCD cells, indicating that calmodulin and calcineurin are not major regulators of vasopressin-induced AQP2 activation.…”

Section: Activators Of Calcium Signalingmentioning

confidence: 99%

“…Analysis of Wnt5a suggested that calcineurin is a key molecule in the activation of AQP2. The importance of calcineurin was confirmed with its direct activator arachidonic acid, which possesses vasopressin-like effects in mpkCCD cells [ 31 ]. Hence, screening for calcineurin activators is a potential therapeutic strategy to develop novel drugs for the treatment of congenital NDI.…”

Section: Activators Of Calcium Signalingmentioning

confidence: 99%

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Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus

Ando

Uchida

2018

Clin Exp Nephrol

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Congenital nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentrating ability. Symptomatic polyuria is present from birth, even with normal release of the antidiuretic hormone vasopressin by the pituitary. Over the last two decades, the aquaporin-2 (AQP2) gene has been cloned and the molecular mechanisms of urine concentration have been gradually elucidated. Vasopressin binds to the vasopressin type II receptor (V2R) in the renal collecting ducts and then activates AQP2 phosphorylation and trafficking to increase water reabsorption from urine. Most cases of congenital NDI are caused by loss-of-function mutations to V2R, resulting in unresponsiveness to vasopressin. In this article, we provide an overview of novel therapeutic molecules of congenital NDI that can activate AQP2 by bypassing defective V2R signaling with a particular focus on the activators of the calcium and cAMP signaling pathways.

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Triple Interface Optimization of Ru‐based Electrocatalyst with Enhanced Activity and Stability for Hydrogen Evolution Reaction

Sun

Niu

et al. 2023

Adv Funct Materials

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A challenging task is to promote Ru atom economy and simultaneously alleviate Ru dissolution during the hydrogen evolution reaction (HER) process. Herein, Ru nanograins (≈1.7 nm in size) uniformly grown on 1T-MoS 2 lace-decorated Ti 3 C 2 T x MXene sheets (Ru@1T-MoS 2 -MXene) are successfully synthesized with three types of interfaces (Ru/MoS 2 , Ru/MXene, and MoS 2 /MXene). It gives high mass activity of 0.79 mA µg Ru −1 at an overpotential of 100 mV, which is ≈36 times that of Ru NPs. It also has a much smaller Ru dissolution rate (9 ng h −1 ), accounting for 22% of the rate for Ru NPs. Electrochemical tests, scanning electrochemical microscopy measurements combined with DFT calculations disclose the role of triple interface optimization in improved activity and stability. First, 2D MoS 2 and MXene can well disperse and stabilize Ru grains, giving larger electrochemical active area. Then, Ru/MoS 2 interfaces weakening H * adsorption energy and Ru/MXene interfaces enhancing electrical conductivity, can efficiently improve the activity. Next, MoS 2 /MXene interfaces can protect MXene sheet edges from oxidation and keep 1T-MoS 2 phase stability during the long-term catalytic process. Meanwhile, Ru@1T-MoS 2 -MXene also displays superior activity and stability in neutral and alkaline media. This work provides a multiple-interface optimization route to develop high-efficiency and durable pH-universal Ru-based HER electrocatalysts.

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Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway

Cited by 56 publications

References 59 publications

AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus

Triple Interface Optimization of Ru‐based Electrocatalyst with Enhanced Activity and Stability for Hydrogen Evolution Reaction

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