LPS-Induced Epithelial-Mesenchymal Transition of Intrahepatic Biliary Epithelial Cells

Zhao, Leilei; Yang, Rigao; Cheng, Long; Wang, Maijian; Jiang, Yan; Wang, Shuguang

doi:10.1016/j.jss.2010.04.059

Cited by 56 publications

(48 citation statements)

References 16 publications

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“…Increased Gram-negative bacteria infection leads to greater release of LPS in colorectal tumor in situ . Previous studies reported that LPS can promote epithelial-mesenchymal transition, cell migration and invasion through NF-kB-Snail signaling [15–17]. LPS can increase lymphangiogenesis involving with VEGF-C, VEGFR-3 and pro-inflammatory cytokines [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-κB/JNK pathways in colorectal cancer

Zhu

Huang

et al. 2016

Oncotarget

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Lipopolysaccharide (LPS) exists in the outer membrane of Gram-negative bacteria. Colorectal normal epithelium and colorectal cancer cells in situ are continuously exposed to LPS from intestinal bacteria, while little is known about the influence of LPS on colorectal cancer progression and metastasis. In this study, we investigated the potential role of LPS on colorectal cancer progression and metastasis as well as the underlying mechanisms. We measured higher LPS concentration in colorectal cancer tissues and even higher LPS concentration in colorectal cancer tissues with lymph node metastasis. LPS significantly enhanced cancer cell motility and promoted human dermal lymphatic endothelial cells' (HDLECs') capacity of tube-like formation in vitro, as well as accelerates lymphangiogenesis and lymph node metastasis in nude mice. Furthermore, we demonstrated LPS notably increased the expression of VEGF-C in a time-dependent and concentration-dependent manner. VEGF-C is a key regulator for lymphangiogenesis and lymph node metastasis. By constructing lentivirus-mediated shVEGF-C cells, VEGF-C down-regulation suppressed LPS' promotive effect on cancer cell motility and HDLEC tube-like formation capacity. In addition, we found TLR4- NF-κB/JNK signal pathways were important for LPS to increase VEGF-C expression. All these result suggested a critical role for LPS in migration, invasion, lymphangiogenesis and lymph node metastasis of colorectal cancer, providing evidence that LPS increased VEGF-C secretion to promote cell motility and lymphangiogenesis via TLR4- NF-κB/JNK signaling.

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-κB/JNK pathways in colorectal cancer

Zhu

Huang

et al. 2016

Oncotarget

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“…Although the exact origin of activated myofibroblasts remains uncertain, emerging evidence suggests that they may derive from epithelial cells by an epithelialemesenchymal transition (EMT) process [6]. Recent studies indicate that lipopolysaccharide (LPS), one of the main pathogens that lead to ALI/ARDS, can induce EMT process in hepatocytes [7], intrahepatic biliary epithelial cells [8] and melanoma cells [9]. However, whether EMT occurs during LPS-induced pulmonary fibrosis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

et al. 2015

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“…However, by means of EndMT, a fibrotic-like spindle-shaped phenotype with non-connected cells is observed along with a-SMA and FSP-1 overexpression, which alters the cytoskeletal organization. [34][35][36][37][38][39][40][41][42][43] Furthermore, acquisition of ECM proteins such as fibronectin and collagen type III is a prominent functional feature of myofibroblasts that changes endothelial functionality. Healthy ECs secrete collagen type IV and low amounts of fibronectin, whereas collagen type I and type III are virtually absent, appearing only after fibrosis has been established and affecting normal endothelial function.…”

mentioning

confidence: 99%

“…The increase in ECM proteins during EndMT alters EC function because it affects the interaction between ligands and membrane receptors, protein turnover, and protein internalization. 34,36,37,[41][42][43][44][45][46][47] In addition, increased cell migration is a major distinctive feature of myofibroblasts. Because EndMT is a cellular mechanism for the conversion of polarized ECs into motile mesenchymal cells, this process is also characterized by the acquisition of migratory features.…”

mentioning

confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

122

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During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

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LPS-Induced Epithelial-Mesenchymal Transition of Intrahepatic Biliary Epithelial Cells

Cited by 56 publications

References 16 publications

Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-κB/JNK pathways in colorectal cancer

Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-κB/JNK pathways in colorectal cancer

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

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