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Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction
- Source :
- American journal of physiology. Renal physiology. 320(5)
- Publication Year :
- 2021
-
Abstract
- Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial BOO (pBOO), we found that rats treated with metformin showed lower baseline pressures with a reduced inflammatory reaction in the early phase (2 wk) after pBOO. The NLR family pyrin domain containing 3 inflammasome pathway was inhibited in pBOO rat bladders with treatment of metformin in the early phase. Metformin reduced the activity of NLR family pyrin domain containing 3 in primary urothelial cells. In the chronic phase (9 wk after pBOO), metformin treatment ameliorated bladder fibrosis and improved the reduced compliance. Treatment with metformin suppressed the activation of Smad3 and compensated the diminished autophagy in 9-wk pBOO rat bladders. Autophagy was inhibited with upregulation of profibrotic proteins in primary fibroblasts from chronic pBOO bladders, which could be restored by administration of metformin. The antifibrotic effects of metformin on fibroblasts were diminished after silencing of AMP-activated protein kinase or light chain 3B. In summary, this study elucidates that oral administration of metformin relieves inflammation in the bladder during the early phase of pBOO. Long-term oral administration of metformin can prevent functional and histological changes in the pBOO rat bladder. The current study suggests that metformin might be used to prevent the development of bladder dysfunction secondary to BOO.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Time Factors
endocrine system diseases
Physiology
Urinary Bladder
030232 urology & nephrology
Urology
Anti-Inflammatory Agents
Inflammation
AMP-Activated Protein Kinases
urologic and male genital diseases
Rats, Sprague-Dawley
03 medical and health sciences
Bladder outlet obstruction
0302 clinical medicine
Downregulation and upregulation
Oral administration
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Cells, Cultured
business.industry
Autophagy
nutritional and metabolic diseases
AMPK
Inflammasome
Fibroblasts
Fibrosis
Metformin
Urinary Bladder Neck Obstruction
Disease Models, Animal
Oxidative Stress
Urodynamics
030104 developmental biology
Cytokines
Female
medicine.symptom
Inflammation Mediators
Urothelium
business
Microtubule-Associated Proteins
medicine.drug
Subjects
Details
- ISSN :
- 15221466
- Volume :
- 320
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Renal physiology
- Accession number :
- edsair.doi.dedup.....cb8acbb213e7ec41381e15b15ae2cc83