Toll-like receptor 4 shRNA attenuates lipopolysaccharide-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells in rats

Tang, Shuli; Jiang, Xiuhan; Wu, L.-C.; Chen, Shifa; Ling, Chen; Jiang, Jichang; Yan, Pengzhan; Wang, Fang; Tu, Kui; Wang, Dianbei; Gu, Jing; Zhao, Leilei

doi:10.1016/j.biopha.2018.08.071

Cited by 13 publications

(13 citation statements)

References 49 publications

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“…It was found that TLR4 signaling could promote EMT induced by lipopolysaccharide in human hepatocellular carcinoma, 49 and TLR4 knockdown attenuated lipopolysaccharide-induced EMT in intrahepatic biliary epithelial cells. 50 Studies also showed that the increase of pro-inflammatory cytokines could trigger the activation of EMT. 51 Therefore, we hypothesized that miR-370-3p might inhibit EMT of UC-CRC in part by regulating TLR4 and its downstream factors.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition</p>

Lin¹,

Wang²,

Qu³

et al. 2020

DDDT

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Introduction: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UCassociated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro. Methods: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×10 8 pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks. Results: We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, β-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelialmesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating β-catenin in colon cancer cells. Conclusion: Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy.

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Section: Discussionmentioning

confidence: 99%

<p>miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition</p>

Lin¹,

Wang²,

Qu³

et al. 2020

DDDT

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“…It is noteworthy that toll-like receptor 4 (TLR4), a receptor for LPS which could enhance TGF-β signaling pathway, has been reported to play a key role in the process of organ fibrogenesis and LPS-induced EMT process (Guillot et al 2004;Seki et al 2007;He et al 2016;Tang et al 2018;Vidya et al 2018). And interestingly, previous studies implicated that cross talks exist between toll-like receptors and integrin αvβ6 (Pittet et al 2013;Jolly et al 2014), so integrin αvβ6 might be a therapeutic target for toll-like receptor-mediated fibrogenesis process.…”

Section: Discussionmentioning

confidence: 99%

Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of Pseudomonas aeruginosa via TGF-β1-Smad2/3 signaling pathway

2019

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Lower respiratory tract infection due to Pseudomonas aeruginosa has become increasingly challenging, resulting in a worse morbidity and mortality. Airway remodeling is a common phenomenon in this process, to which epithelial-mesenchymal transition (EMT) may contribute as an important promoter. Previous studies showed that epithelium-specific integrin αvβ6mediated EMT was involved in pulmonary fibrosis via transforming growth factor-β1 (TGF-β1) signaling, but whether integrin αvβ6 plays a role in the P. aeruginosa-associated airway remodeling remains unknown. BEAS-2B cells were incubated with lipopolysaccharide (LPS) from P. aeruginosa in the presence or the absence of integrin αvβ6-blocking antibodies. Morphologic changes were observed by an inverted microscopy. The EMT markers were detected using Western blotting and immunofluorescence. The activation of TGF-β1-Smad2/3 signaling pathway was assessed. Furthermore, matrix metalloproteinase (MMP)-2 and-9 in the medium were measured using ELISA. P. aeruginosa's LPS decreased the expression of the epithelial marker Ecadherin and promoted the mesenchymal markers, vimentin and α-smooth muscle actin in BEAS-2B cells. The expression of integrin αvβ6 was significantly increased during EMT process. Blocking integrin αvβ6 could attenuate P. aeruginosa's LPSinduced EMT markers' expression via TGF-β1-Smad2/3 signaling pathway. Furthermore, blocking integrin αvβ6 could prevent morphologic changes and oversecretion of MMP-2 and-9. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of P. aeruginosa via TGF-β1-Smad2/3 signaling pathway and might be a promising therapeutic target for P. aeruginosa-associated airway remodeling.

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“…High CD31 expression is often found in tumor tissues by immunohistochemistry and associated with a poor prognosis among cancer patients (Basilio-de-Oliveira and Pannain 2015 ; Cao et al 2018 ), but high CD31 secretion by tumor cells has rarely been analyzed by protein microarray or ELISA, as observed in this study. VE-cadherin, also known as cadherin-5, is an adhesion molecule uniquely expressed in endothelial cells that has been used to assess microvessels and angiogenesis in human breast cancer (Zhao et al 2018 ; Tang et al 2018 ; Zhou et al 2018 ). High expression of VE-cadherin in the tumor correlates with poor prognosis in human gastric cancer (Higuchi et al 2017 ), but the level of soluble VE-cadherin has not been detected in cancer cells or tissues.…”

Section: Discussionmentioning

confidence: 99%

Effects of VEGFR1+ hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells

Meng

Luo

et al. 2018

J Cancer Res Clin Oncol

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The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1) + CD133 + hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung. We also established a highly metastatic MDA-MB-435s (MDA-MB-435s-HM) cell line from the mouse model. Changes in protein profiles in different culture conditions were investigated by protein microarray analysis. The levels of CXC chemokine ligand 16, interleukin (IL)-2Rα, IL-2Rγ, matrix metalloproteinase (MMP)-1, MMP-9, platelet-derived growth factor receptor (PDGFR)-α, stromal cell-derived factor (SDF)-1α, transforming growth factor (TGF)-β, platelet endothelial cell adhesion molecule (PECAM)-1 and vascular endothelial (VE)-cadherin were significantly greater (> fivefold) in the culture medium from MDA-MB-435s-HM cells than in that from MDA-MB-435s cells. Moreover, the levels of MMP-9, PDGFR-α, and PECAM-1 were significantly greater in the co-culture medium of MDA-MB-435s-HM cells and CD133 + HPCs than in that from MDA-MB-435s-HM cells. Differentially expressed proteins were validated by enzyme-linked immunosorbent assay, and expression of their transcripts was confirmed by quantitative real-time polymerase chain reaction. Moreover, inhibition of MMP-9, PDGFR-α, and PECAM-1 by their specific inhibitors or antibodies significantly decreased cell migration, delayed lung metastasis, and decreased recruitment of VEGFR1 + CD133 + HPCs into lung. Intra-hepatic growth of HPCs enhanced the invasive growth of MDA-MB-435s-HM cells in the liver. Our data indicate that VEGFR1 + CD133 + HPCs contribute to lung metastasis. Electronic supplementary material The online version of this article (10.1007/s00432-018-2802-6) contains supplementary material, which is available to authorized users.

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Toll-like receptor 4 shRNA attenuates lipopolysaccharide-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells in rats

Cited by 13 publications

References 49 publications

<p>miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition</p>

<p>miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition</p>

Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of Pseudomonas aeruginosa via TGF-β1-Smad2/3 signaling pathway

Effects of VEGFR1+ hematopoietic progenitor cells on pre-metastatic niche formation and in vivo metastasis of breast cancer cells

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