Tumor necrosis factor‐alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter

Shinohara, Mayuka; Sumino, Yasuhiro; Sato, Fuminori; Kiyono, Tohru; Hashimoto, Naohiro; Mimata, Hiromitsu

doi:10.1111/iju.13330

Cited by 10 publications

(4 citation statements)

References 29 publications

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“…Enrichment analysis of the KEGG pathway reveals involvement in various pathways, including tumor, inflammation, and endocrine systems. Shinohara et al [50] found that TNF-α has an inhibitory effect on urethral smooth muscle cells, suggesting that inhibiting TNF-α may have some effect on potential treatments for urinary incontinence.…”

Section: Discussionmentioning

confidence: 99%

Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

Ma,

Shen,

Yang

et al. 2024

JCMP

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Objective: Investigating how Qing-e pill aids in managing stress urinary incontinence through network pharmacology. Methods: Utilizing the TCM system's pharmacological database and analytical framework (TCMSP), along with literature exploration, the active components and their respective targets for Qing-e pill were identified, leading to the creation of a network of compound TCM - active ingredients - targets. The focus of SUI was identified using the GeneCards and OMIM databases. The active ingredient SUI-target network model was developed and examined using the Cytoscape 3.10.1 software. The protein interaction network (PPI) was created using the STRING database, incorporating gene ontology functional annotation (GO) and Tokyo Genome Encyclopedia (KEGG) pathway enrichment analysis on key targets through DAVID online, with molecular docking performed using Surflex software. Results: Screening yielded 86 active components, 461 possible targets, 2551 SUI targets, and 187 typical targets for Qing-e pill and SUI. The outcomes of network analysis revealed Qing-e pill's primary targets for SUI treatment were AKT1, IL6, JUN, TNF, HSP90AA1, ESR1, CTNNB1, EGFR, among others. The primary biological mechanisms encompassed reactions to lipopolysaccharide, molecules originating from bacteria, metal ions, growth of epithelial cells, and the control of membrane potential, among others. KEGG enrichment primarily aims to utilize the AGE-RAGE signaling pathway in treating a range of conditions, including diabetes complications, prostate cancer, fluid shear stress, atherosclerosis, lipid and atherosclerosis, IL-17 signaling pathway, and more. Conclusion: Initially, network pharmacology shed light on the foundational materials and operational methods of Qing-e pill in treating SUI, offering a theoretical foundation for their clinical use.

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Section: Discussionmentioning

confidence: 99%

Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

Ma,

Shen,

Yang

et al. 2024

JCMP

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“…Previous studies have explored the impact of inflammation on UI. Shinohara et al demonstrated that TNF-α suppressed the myogenic differentiation of human urethral rhabdosphincter cells, suggesting that TNF-α may be a risk factor of SUI in the elderly [ 24 ]. Additionally, inflammation also plays a role in overactive bladder (OAB) associated with UI.…”

Section: Discussionmentioning

confidence: 99%

The association between the metabolic score for insulin resistance (METS-IR) index and urinary incontinence in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2001–2018

Cao,

Meng,

Lin

et al. 2023

Diabetol Metab Syndr

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Background The association between insulin resistance and urinary incontinence (UI) has not been investigated widely. The purpose of this study is to assess the relationship between a novel indicator for assessing insulin resistance the metabolic score for insulin resistance (METS-IR) index and urinary incontinence (UI). Methods This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2001–2018. Weighted multivariable logistic regression models were conducted to explore the association of METS-IR index with three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. Smooth curve fitting was utilized to investigate the linear relationship. Subgroup analysis was used to examine the stability of the connection between METS-IR index and UI in different stratifications. Results A total of 17,474 participants were included in this study, of whom 23.76% had SUI, 20.05% had UUI, and 9.59% had MUI. METS-IR index was positively associated with three types of UI with full adjustment [SUI: odds ratio (OR) = 1.023, 95% confidence interval (CI) 1.019–1.027; UUI: OR = 1.015, 95% CI 1.011–1.019; MUI: OR = 1.020, 95% CI 1.016–1.025, all p < 0.001]. After transferring METS-IR index into a categorical variable by quartiles, the positive connection between METS-IR index and UI was still observed in the highest METS-IR group compared to the lowest METS-IR interval (SUI: OR = 2.266, 95% CI 1.947–2.637, p < 0.001; UUI: OR = 1.534, 95% CI 1.344–1.750, p < 0.001; MUI: OR = 2.044, 95% CI 1.707–2.448, p < 0.001). The analysis of smooth curves fitting showed that METS-IR index was positively linearly related to three types of UI. Moreover, the association between METS-IR index and SUI was more significant in females compared to males (p for interaction < 0.05). Conclusion An elevated METS-IR index was related to increased risks of three types of UI (SUI, UUI, and MUI) in the United States population. METS-IR index was more significantly connected to SUI in females than males. The association between insulin resistance and UI needs to be explored with more studies.

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“…In addition, TNF-α was shown to inhibit the myogenic differentiation of human RS progenitor cells through the PI3K and p38-mitogen activated protein-kinase (MAPK) pathways in a dose-dependent manner. Based on this, the research group established an immortalized human RS cell line to identify a possible new therapy for SUI through autologous transplantation of muscle or adipose-derived stem cells ( Shinohara et al, 2017 ).…”

Section: Muscle-derived Factorsmentioning

confidence: 99%

Advances in the molecular pathogenesis and cell therapy of stress urinary incontinence

Wang

Zhang²,

Lu³

2023

Front. Cell Dev. Biol.

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Stress urinary incontinence (SUI) is very common in women. It affects patients’ mental and physical health, and imposed huge socioeconomic pressure. The therapeutic effect of conservative treatment is limited, and depends heavily on patient persistence and compliance. Surgical treatment often brings procedure-related adverse complications and higher costs for patients. Therefore, it is necessary to better understand the potential molecular mechanisms underlying stress urinary incontinence and develop new treatment methods. Although some progress has been made in the basic research in recent years, the specific molecular pathogenic mechanisms of SUI are still unclear. Here, we reviewed the published studies on the molecular mechanisms associated with nerves, urethral muscles, periurethral connective tissue and hormones in the pathogenesis of SUI. In addition, we provide an update on the recent progresses in research on the use of cell therapy for treating SUI, including research on stem cells therapy, exosome differentiation and gene regulation.

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Tumor necrosis factor‐alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter

Abstract: Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence.

Cited by 10 publications

References 29 publications

Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

The association between the metabolic score for insulin resistance (METS-IR) index and urinary incontinence in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2001–2018

Advances in the molecular pathogenesis and cell therapy of stress urinary incontinence

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