Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction

Abstract

Alteration of bladder morphology and function was the most important consequence of bladder outlet obstruction (BOO). Using a rat model of partial bladder outlet obstruction (pBOO), we found that rats treated with metformin showed lower baseline pressures with reduced inflammatory reaction in early phase (2 weeks) after pBOO. NLRP3 inflammasome pathway was inhibited in pBOO rat bladders with the treatment of metformin in early phase. Metformin reduced the activity of NLRP3 in primary urothelial cells. In chronic phase (9 weeks 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-week pBOO rat bladder. Autophagy was inhibited with upregulation of pro-fibrotic proteins in primary fibroblasts from chronic pBOO bladder, which could be restored by administration of metformin. The anti-fibrotic effects of metformin on fibroblasts were diminished after silencing AMPK or LC3B. In summary, this study elucidates that oral administration of metformin relives inflammation in bladder during 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.

RETRACTED ARTICLE: Circular RNA Plasmacytoma Variant Translocation 1 (CircPVT1) knockdown ameliorates hypoxia-induced bladder fibrosis by regulating the miR-203/Suppressor of Cytokine Signaling 3 (SOCS3) signaling axis

“…This is one of limitations of the present study. In another aspect, BOO surgery used in this study caused bladder wall remodeling in rats, including hypertrophy and fibrosis, which is also the major characters of human BOO [ 50 ], meanwhile, this model has been applied in many similar reports [ 51 , 52 ]. We have demonstrated a role of circPVT1 on BOO development in animal model and cell-based model, but its application to human BOO were still obscure.…”

RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy

“…Autophagy is a highly regulated catabolic process that maintains cellular homeostasis in response to various damaged, defective, or unwanted stimuli ( Geir et al, 2005 ; Li et al, 2016 ; Daniel et al, 2018 ; Nam et al, 2019 ). Increasing evidence suggests that autophagy is closely related the bladder remodeling secondary to BOO due to its double-edged sword role in pro-cell survival and the pro-cell death properties ( Chen et al, 2021 ). Our previous study has demonstrated that autophagy regulated the biological function of BSMCs under HP ( Chen et al, 2020b ).…”

Are C-reactive protein, neutrophil to lymphocyte, platelet to lymphocyte ratios, and mean platelet volume related to the severity of idiopathic carpal tunnel syndrome?

“…With regard 907 to metformin effect on the bladder contractility, there were only few meeting reports and there was insufficient studies on the mechanism of action of metformin on the urinary bladder of rats. [9,10,11]. Studied that differential effects of metformin in rats' urinary bladder and other different tissues.…”