Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation

Lai, Jianyu; Ge, Manqing; Shen, Shunyao; Yang, Lu; Jin, Tao; Cao, Dehong; Xu, Hang; Zheng, Xiaonan; Qiu, Shi; Wang, Kunjie; Wei, Qiang; Li, Hong; Ai, Jianzhong

doi:10.1016/j.bbadis.2019.05.008

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…NF-kB is a well-known transcription factor in the regulation of the inflammatory response induced by LPS. [23][24][25][26][27][28][29] Immune cells contain Toll-like receptors (TLRs) to which LPS can bind to trigger an immune response leading to the activation of the NF-kB transcription factor. The activation and synthesis of this transcription factor lead to the transcription and synthesis of pro-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

Ahmed

Amin

Sun

et al. 2022

Exp Biol Med (Maywood)

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Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.

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Section: Discussionmentioning

confidence: 99%

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

Ahmed

Amin

Sun

et al. 2022

Exp Biol Med (Maywood)

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“…As the upstream target of JMJD3, NF-κB regulates inflammatory gene expression in vascular endothelial cells (26). In addition, cystitis promotes NF-κB pathway activation and JMJD3 expression, thereby inducing proliferation of human bladder smooth muscle cells and ECM deposition (27). It is worth noting that YAP1 was shown to inhibit the negative regulatory factor of NF-κB USP31 and induce excessive tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

YAP1 promotes high glucose‑induced inflammation and extracellular matrix deposition in glomerular mesangial cells by modulating NF‑κB/JMJD3 pathway

Wang

Zhang

2021

Exp Ther Med

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Diabetic nephropathy (DN) is one of the most serious microvascular complications of late-stage diabetes. Glomerular mesangial cell (GMC) proliferation and excessive extracellular matrix (ECM) deposition are the main pathological characteristics associated with the occurrence and development of DN. Yes-associated protein 1 (YAP1) can bind to several transcription factors and is associated with the development of various diseases. However, the effects of YAP1 on DN remain unclear. The aim of the present study was to explore the regulatory effect and potential mechanism of YAP1 in glucose-induced inflammation and ECM deposition in high-glucose-treated GMCs.In the present study, HBZY-1 cell models treated with high glucose were constructed, and the effects of YAP1 on the proliferation, inflammation, ECM deposition and fibrosis of HBZY-1 cells were detected. The results showed that YAP1 was highly expressed in HBZY-1 cells treated with high glucose and that YAP1 silencing decreased cell viability, the levels of inflammatory cytokines, ECM deposition and the degree of fibrosis in cells. Further experiments revea led t hat N F-κ B/Ju monji doma i n-cont a i n i ng protein D3 (JMJD3) signaling pathway inhibitors alleviated the promoting effect of YAP1 overexpression on inflammatory response and ECM deposition in HBZY-1 cells treated with high glucose. In conclusion, it was demonstrated that YAP1 can promote high glucose-induced inflammation and ECM deposition by activating the NF-κB/JMJD3 signaling pathway in GMCs.

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“…Another possible link between inflammation and LUTS is inflammation-induced bladder fibrosis. Lai et al [9] found that inflammation activated the NF-jB-JMJD3 signaling and promoted proliferation and extracellular matrix deposition of human bladder smooth muscle cells. Further research is warranted to investigate whether the association between LUTS and DII results from inflammation-induced prostatic enlargement or bladder dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a diet with high inflammatory potential may influence prostatic inflammation and lead to LUTS secondary to BPH. Recent studies [8,9] have also shown that inflammation plays a key role in the pathogenesis of bladder fibrosis, resulting in compromised bladder capacity and symptoms like urinary frequency and urgency. The dietary inflammatory index (DII) is a quantitative index to represent the individual intake of pro-inflammatory diets.…”

Section: Introductionmentioning

confidence: 99%

Association of the inflammatory potential of diet and lower urinary tract symptoms among men in the United States

et al. 2021

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Background: Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. Methods: We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. Results: We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). Conclusions: Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.

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Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation

Cited by 19 publications

References 29 publications

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

YAP1 promotes high glucose‑induced inflammation and extracellular matrix deposition in glomerular mesangial cells by modulating NF‑κB/JMJD3 pathway

Association of the inflammatory potential of diet and lower urinary tract symptoms among men in the United States

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