Statin pretreatment inhibits the lipopolysaccharide‐induced epithelial‐mesenchymal transition via the downregulation of toll‐like receptor 4 and nuclear factor‐κB in human biliary epithelial cells

Kim, Yangmi; Lee, Eun Jeoung; Jang, Hee Kyung; Kim, Chan Hyung; Kim, Dae‐Ghon; Han, Joung Ho; Park, Seon Mee

doi:10.1111/jgh.13230

Cited by 19 publications

(16 citation statements)

References 45 publications

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“…EMT of biliary epithelial cells plays a critical role in biliary fibrosis. Simvastatin could prevent biliary fibrosis involved in the EMT progress of biliary epithelial cells that was related to the inhibition of Twist1 expression , which indicates that Twist1 may also be a feasible target for biliary fibrosis.…”

Section: Twist1 and Fibrotic Diseasesmentioning

confidence: 95%

Emerging role of Twist1 in fibrotic diseases

Ning

Zhang

et al. 2018

J Cellular Molecular Medi

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Epithelial–mesenchymal transition (EMT) is a pathological process that occurs in a variety of diseases, including organ fibrosis. Twist1, a basic helix–loop–helix transcription factor, is involved in EMT and plays significant roles in various fibrotic diseases. Suppression of the EMT process represents a promising approach for the treatment of fibrotic diseases. In this review, we discuss the roles and the underlying molecular mechanisms of Twist1 in fibrotic diseases, including those affecting kidney, lung, skin, oral submucosa and other tissues. We aim at providing new insight into the pathogenesis of various fibrotic diseases and facilitating the development of novel diagnostic and therapeutic methods for their treatment.

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Section: Twist1 and Fibrotic Diseasesmentioning

confidence: 95%

Emerging role of Twist1 in fibrotic diseases

Ning

Zhang

et al. 2018

J Cellular Molecular Medi

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“…We next sought to examine the upstream signals that orchestrate LPS-induced MTOR activation in HBE cells. TLR4 is a well-recognized membrane receptor for LPS and it is also abundantly expressed in epithelial cells; [14][15][16] we therefore attempted to investigate the role of TLR4 signals in regulation of LPSinduced MTOR activation. As expected, the treatment with LPS upregulated the levels of TLR4 and MYD88 in HBE cells (Fig.…”

Section: Lps Activates Mtor Via Upstream Tlr4 (Toll-like Receptor 4) mentioning

confidence: 99%

Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury

et al. 2016

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MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

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“…For example, deoxycholic acid (DCA) is able to enhance the transcription of enzymes in cancer associated fibroblasts (CAFs) [ 20 ]. Lithocholic acid (LCA) can control T-Helper 17 (Th17) and regulatory T cells (Treg) differentiation [ 21 ], while lipopolysaccharide (LPS) can act on epithelial cells, promoting the induction of the EMT [ 22 , 23 ], and is also able to activate the vascular endothelial growth factor (VEGF) receptor, inducing angiogenesis [ 24 ].…”

Section: Microbiome Contribute To Cancer Hallmarks Modulating Tumomentioning

confidence: 99%

“…LPS has been shown to have a promoter role in the induction of EMT as well in invasion and metastasis in human intrahepatic biliary epithelial cells by upregulating the expression of transforming growth factor beta 1 (TGF-β1) as a result of biliary infection. However, this process remains reversible because EMT can be blocked through TGF-β1 inhibition, but also by using statins, driving the downregulation of TLR4 expression and NF-kB phosphorylation [ 22 , 23 ] ( Figure 1 ).…”

Section: Toxin: Lipopolysaccharide (Lps)mentioning

confidence: 99%

Microbiota-Derived Metabolites in Tumor Progression and Metastasis

Rossi

Vergara

Fanini

et al. 2020

IJMS

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Microbial communities and human cells, through a dynamic crosstalk, maintain a mutualistic relationship that contributes to the maintenance of cellular metabolism and of the immune and neuronal systems. This dialogue normally occurs through the production and regulation of hormonal intermediates, metabolites, secondary metabolites, proteins, and toxins. When the balance between host and microbiota is compromised, the dynamics of this relationship change, creating favorable conditions for the development of diseases, including cancers. Microbiome metabolites can be important modulators of the tumor microenvironment contributing to regulate inflammation, proliferation, and cell death, in either a positive or negative way. Recent studies also highlight the involvement of microbiota metabolites in inducing epithelial–mesenchymal transition, thus favoring the setup of the metastatic niche. An investigation of microbe-derived metabolites in “liquid” human samples, such as plasma, serum, and urine, provide further information to clarify the relationship between host and microbiota.

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Statin pretreatment inhibits the lipopolysaccharide‐induced epithelial‐mesenchymal transition via the downregulation of toll‐like receptor 4 and nuclear factor‐κB in human biliary epithelial cells

Cited by 19 publications

References 45 publications

Emerging role of Twist1 in fibrotic diseases

Emerging role of Twist1 in fibrotic diseases

Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury

Microbiota-Derived Metabolites in Tumor Progression and Metastasis

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