AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis.

Zhang X, Yao J, Gao K, Chi Y, Mitsui T, Ihara T, Sawada N, Kamiyama M, Fan J, Takeda M

Scientific reports25 Jan 2016Cited by 24 (Europe PMC)

PMID26806558PMCIDPMC4726257DOI10.1038/srep19708PepBankPUB-26806558

Summary

Bladder voiding dysfunction is closely related to local oxidation, inflammation, and enhanced channel activities. Given that the AMP-activated protein kinase (AMPK) has anti-oxidative, anti-inflammatory and channel-inhibiting properties, we examined whether and how AMPK affected bladder activity. AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation. Downregulation of CREB with siRNA increased Cx43 expression. A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity. AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs. In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction. Further analysis comparing the responses of the wild-type (Cx43(+/+)) and heterozygous (Cx43(+/-)) Cx43 mice to cyclophosphamide revealed that the Cx43(+/-) mice retained a relatively normal micturition pattern compared to the Cx43(+/+) mice. Taken together, our results indicate that AMPK inhibits Cx43 in BSMCs and improves bladder activity under pathological conditions. We propose that strategies that target AMPK can be developed as novel therapeutic approaches for treating bladder dysfunction.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice, AICAR attenuated cyclophosphamide-induced bladder oxidation.
In plain wordsIn mice, AICAR reduced bladder oxidation caused by cyclophosphamide.
Peptide
AICAR (acadesine)
Outcome
DecreaseBladder oxidation
Study
mousen: not reported in source
cyclophosphamide-induced cystitis
Outcome group
Oxidative stress · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction.
1 context sentence(design, population, supporting numbers)
Title · context
AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis.
Show in the study text Report a problemFND-2680655811
02AnimalAnimal study (in vivo)Efficacy outcome
In mice, AICAR attenuated cyclophosphamide-induced bladder inflammation.
In plain wordsIn mice, AICAR reduced bladder inflammation caused by cyclophosphamide.
Peptide
AICAR (acadesine)
Outcome
DecreaseBladder inflammation
Study
mousen: not reported in source
cyclophosphamide-induced cystitis
Outcome group
Inflammation markers · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction.
1 context sentence(design, population, supporting numbers)
Title · context
AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis.
Show in the study text Report a problemFND-2680655812
03AnimalAnimal study (in vivo)Mechanism
In mice, AICAR attenuated cyclophosphamide-induced bladder Cx43 expression.
In plain wordsIn mice, AICAR reduced bladder Cx43 expression induced by cyclophosphamide.
Peptide
AICAR (acadesine)
Outcome
DecreaseBladder Cx43 expression
Study
mousen: not reported in source
cyclophosphamide-induced cystitis
Outcome group
Receptor activity and mechanism · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction.
1 context sentence(design, population, supporting numbers)
Title · context
AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis.
Show in the study text Report a problemFND-2680655813
04AnimalAnimal study (in vivo)Efficacy outcome
In mice, AICAR attenuated cyclophosphamide-induced voiding dysfunction.
In plain wordsIn mice, AICAR reduced urination problems caused by cyclophosphamide.
Peptide
AICAR (acadesine)
Outcome
DecreaseVoiding dysfunction
Study
mousen: not reported in source
cyclophosphamide-induced cystitis
Outcome group
Urinary continence and bladder function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
In vivo administration of the AMPK agonist AICAR attenuated cyclophosphamide-initiated bladder oxidation, inflammation, Cx43 expression and voiding dysfunction.
1 context sentence(design, population, supporting numbers)
Title · context
AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis.
Show in the study text Report a problemFND-2680655814

Studies that did not test the peptide alone10

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

05AnimalNot a test of AICAR (acadesine) aloneOther designActivity measurement
In the bladder functional analysis, AMPK activation weakened bladder capacity.
In plain wordsIn the bladder functional analysis, AMPK activation reduced bladder capacity.
Peptide
AICAR (acadesine)
Outcome
DecreaseBladder capacity
Study
n: not reported in source
Outcome group
Urinary continence and bladder function · Kidney and urinary
Source sentences
Summary
A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655808
06LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, three AMPK agonists decreased Cx43 expression.
In plain wordsIn cells from rat bladders, three AMPK agonists reduced Cx43 expression.
Peptide
AICAR (acadesine)
Outcome
DecreaseCx43 expression
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655801
07LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Activity measurement
In rat bladder smooth muscle cells, three AMPK agonists decreased Cx43 function.
In plain wordsIn cells from rat bladders, three AMPK agonists reduced Cx43 function.
Peptide
AICAR (acadesine)
Outcome
DecreaseCx43 function
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655802
08LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, activation with three AMPK agonists was associated with reduced CREB phosphorylation.
In plain wordsIn cells from rat bladders, activation with three AMPK agonists was linked to reduced CREB phosphorylation.
Peptide
AICAR (acadesine)
Outcome
DecreaseCREB phosphorylation
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655803
09LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, activation with three AMPK agonists was associated with reduced Cx43 promoter activity.
In plain wordsIn cells from rat bladders, activation with three AMPK agonists was linked to reduced Cx43 promoter activity.
Peptide
AICAR (acadesine)
Outcome
DecreaseCx43 promoter activity
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655804
10LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, activation with three AMPK agonists was associated with reduced Cx43 mRNA expression.
In plain wordsIn cells from rat bladders, activation with three AMPK agonists was linked to reduced Cx43 mRNA expression.
Peptide
AICAR (acadesine)
Outcome
DecreaseCx43 mRNA expression
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655805
11LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, activation with three AMPK agonists was not associated with reduced Cx43 degradation.
In plain wordsIn cells from rat bladders, activation with three AMPK agonists was not linked to reduced Cx43 degradation.
Peptide
AICAR (acadesine)
Outcome
No significant changeCx43 degradation
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655806
12LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Activity measurement
In rat bladder smooth muscle cells, AMPK activation weakened contraction.
In plain wordsIn cells from rat bladders, AMPK activation reduced contraction.
Peptide
AICAR (acadesine)
Outcome
DecreaseBladder smooth muscle cell contraction
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Urinary continence and bladder function · Kidney and urinary
Source sentences
Summary
A functional analysis revealed that AMPK weakened BSMC contraction and bladder capacity.
1 context sentence(design, population, supporting numbers)
Summary · context
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655807
13LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, AMPK activation counteracted the IL-1β-induced increase in Cx43.
In plain wordsIn cells from rat bladders, AMPK activation reduced the Cx43 increase induced by IL-1β.
Peptide
AICAR (acadesine)
Outcome
DecreaseIL-1β-induced Cx43 increase
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs.
1 context sentence(design, population, supporting numbers)
Summary · context
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655809
14LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In rat bladder smooth muscle cells, AMPK activation counteracted the TNFα-induced increase in Cx43.
In plain wordsIn cells from rat bladders, AMPK activation reduced the Cx43 increase induced by TNFα.
Peptide
AICAR (acadesine)
Outcome
DecreaseTNFα-induced Cx43 increase
Study
ratn: not reported in source
bladder smooth muscle cells
Outcome group
Receptor activity and mechanism · Kidney and urinary
Source sentences
Summary
AMPK also counteracted the IL-1β- and TNFα-induced increase in Cx43 in BSMCs.
1 context sentence(design, population, supporting numbers)
Summary · context
AMPK activation in rat bladder smooth muscle cells (BSMCs) using three different AMPK agonists resulted in a decrease in connexin43 (Cx43) expression and function, which was associated with reduced CREB phosphorylation, Cx43 promoter activity and mRNA expression, but not Cx43 degradation.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2680655810

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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