Transient receptor potential vanilloid-type 2 targeting on stemness in liver cancer

Hu, Zecheng; Cao, Xiaocheng; Yu, Fang; Liu, Guoxing; Xie, Chengzhi; Ke, Qing; Lei, Xiaohua; Cao, Zhenyu; Du, Huihui; Cheng, Xiangding; Xu, Xundi

doi:10.1016/j.biopha.2018.06.029

Cited by 37 publications

(24 citation statements)

References 35 publications

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“…Abnormal expres-sion of TRPV and alteration of its channel activity are associated with many diseases 6 . We previously reported that TRPV channels are important in the development of hepatocellular carcinoma 8,9 , and recent studies noted that TRPV4 expression was significantly increased in liver fibrotic tissues. Blocking the TRPV4 channels of hepatic stellate cells with selective antagonists significantly inhibits their proliferation 11,12 , perhaps because of autophagymediated apoptosis.…”

Section: Resultsmentioning

confidence: 97%

Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Zhang

et al. 2019

J Nippon Med Sch

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Background: Transient receptor potential vanilloid 4 (TRPV4) is a member of the TRP channel family and is involved in diverse physiological and pathological processes. Accumulating evidence from in vitro studies indicates that TRPV4 has a potential role in liver fibrosis, but its precise role in the pathophysiological development of this condition is unclear. Exogenous interventions and endogenous reactions should be considered. Methods:This study used a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis to investigate the effects of intraperitoneal injection of the novel TRPV4 channel selective agonist GSK1016790A (GSK) and antagonist HC-067047 (HC). Results:As compared with the CCl4 group, collagen fiber deposition and alpha-smooth muscle actin (α-SMA) levels were markedly higher and hepatic lobule disorganization was worse in the CCl4+GSK group, while collagen fiber deposition was significantly lower and hepatic lobule disorganization was less severe in the CCl4+HC group. Conclusions:The present findings suggest that activation of TRPV4 channels worsens liver fibrosis and that inhibition of TRPV4 channels may alleviate liver fibrosis in vivo.

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Section: Resultsmentioning

confidence: 97%

Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Zhang

et al. 2019

J Nippon Med Sch

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“…LCSLCs are considered to be good targets for liver cancer therapy, as they exhibit stem cell properties and are of a highly tumorigenic nature. Therefore, TRPV2 was proposed to be a potential target in hepatoma therapy [86]. Notably, reduced expression of TRPV2 mRNA and protein in poorly differentiated tumors in comparison to higher differentiated hepatoma [78] supports the idea that reduced TRPV2 expression promotes the stem-cell features of hepatoma cells during the early stages of tumor development [86].…”

Section: Liver Cancermentioning

confidence: 91%

TRP Channels in Digestive Tract Cancers

Stokłosa

Borgström

Kappel

et al. 2020

IJMS

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Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.

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“…[80] Therefore human hepatoma HepG2 cell line was used as a representative model of the human liver that display a high degree of morphological and functional differentiation to generate reproducible results. [81] To mimicking a permanent activation of both important phosphorylation sites of RIPK3 (Ser199, Ser227), mutation of the serine residue to aspartic acid (Asp) promoted the IL-8 secretion significantly especially when both phosphorylation sites were mutated to activating Asp residue (Fig. 4B).…”

Section: Bile Acids Are Sensitive To Affect Ripk3 Activation That Indmentioning

confidence: 99%

RIPK3 promoter hypermethylation in hepatocytes protects from bile acid induced inflammation and necroptosis

Hoff¹,

Xiong

Kammann

et al. 2021

Preprint

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Background & AimsNecroptosis facilitates cell death in a controlled manner and is employed by many cell types following injury. It plays a major role in various liver diseases, albeit the cell type-specific regulation of necroptosis in the liver and especially hepatocytes has not yet been conceptualized.Approaches & ResultsHere, we demonstrate that DNA methylation suppresses RIPK3 expression in human hepatocytes and HepG2 cells. In diseases leading to cholestasis the RIPK3 expression is induced in mice and humans in a cell-type specific manner. Over-expression of RIPK3 in HepG2 cells leads immediately to RIPK3 activation by phosphorylation that is further modulated by different bile acids.ConclusionBile acids mediated RIPK3 activation facilitates the secretion and expression of IL-8 via the JNK-pathway, suggesting hepatocytes suppress RIPK3 expression to protect themselves from bile acid induced necroptosis and inflammation but in chronical liver diseases associated with cholestasis induction of RIPK3 expression may be an early event signaling danger and repair through release of IL-8.Graphical abstract

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Transient receptor potential vanilloid-type 2 targeting on stemness in liver cancer

Cited by 37 publications

References 35 publications

Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Pharmacological Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice

TRP Channels in Digestive Tract Cancers

RIPK3 promoter hypermethylation in hepatocytes protects from bile acid induced inflammation and necroptosis

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