scholarly journals Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-β1/Smad2 pathway in RLE-6TN cells

2017 ◽  
Vol 6 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Hong Chen ◽  
Feng-ping Wu ◽  
Yong-zhen Yang ◽  
Xiu-ying Yu ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Epithelial To Mesenchymal Transition ◽  
Cigarette Smoke Extract ◽  
Phospholipid Transfer Protein ◽  
Mesenchymal Transition ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Tgf Β1

Aim: The role of phospholipid transfer protein (PLTP) in the pathogenesis of the cigarette smoke extract (CSE)-induced epithelial-to-mesenchymal transition (EMT) has not been well described.

scholarly journals Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein

2021 ◽  
Vol 12 ◽  
Author(s):  
Maxime Nguyen ◽  
Gaëtan Pallot ◽  
Antoine Jalil ◽  
Annabelle Tavernier ◽  
Aloïs Dusuel ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Central Compartment ◽  
Phospholipid Transfer Protein ◽  
Wild Type ◽  
Transfer Protein ◽  
Early Arrival ◽  
Phospholipid Transfer ◽  
Pass Through ◽  
Lps Binding

IntroductionDuring peritonitis, lipopolysaccharides (LPS) cross the peritoneum and pass through the liver before reaching the central compartment. The aim of the present study was to investigate the role of lipoproteins and phospholipid transfer protein (PLTP) in the early stages of LPS detoxification.Material and MethodsPeritonitis was induced by intra-peritoneal injection of LPS in mice. We analyzed peritoneal fluid, portal and central blood. Lipoprotein fractions were obtained by ultracentrifugation and fast protein liquid chromatography. LPS concentration and activity were measured by liquid chromatography coupled with mass spectrometry and limulus amoebocyte lysate. Wild-type mice were compared to mice knocked out for PLTP.ResultsIn mice expressing PLTP, LPS was able to bind to HDL in the peritoneal compartment, and this was maintained in plasma from portal and central blood. A hepatic first-pass effect of HDL-bound LPS was observed in wild-type mice. LPS binding to HDL resulted in an early arrival of inactive LPS in the central blood of wild-type mice.ConclusionPLTP promotes LPS peritoneal clearance and neutralization in a model of peritonitis. This mechanism involves the early binding of LPS to lipoproteins inside the peritoneal cavity, which promotes LPS translocation through the peritoneum and its uptake by the liver.

scholarly journals A-Kinase Anchoring Proteins Diminish TGF-β1/Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 356 ◽  
Author(s):  
Haoxiao Zuo ◽  
Marina Trombetta-Lima ◽  
Irene H. Heijink ◽  
Christina H. T. J. van der Veen ◽  
Laura Hesse ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cigarette Smoke ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Epithelial Cell Line ◽  
Intracellular Camp ◽  
Mesenchymal Transition ◽  
Anchoring Proteins ◽  
Tgf Β1 ◽  
E Cadherin

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies regarding their therapeutic value in the lung EMT process are lacking. The human bronchial epithelial cell line (BEAS-2B) and primary human airway epithelial (pHAE) cells were exposed to TGF-β1. Epithelial (E-cadherin, ZO-1) and mesenchymal markers (collagen Ӏ, α-SMA, fibronectin) were analyzed (mRNA, protein). ELISA measured TGF-β1 release. TGF-β1-sensitive AKAPs Ezrin, AKAP95 and Yotiao were silenced while using siRNA. Cell migration was analyzed by wound healing assay, xCELLigence, Incucyte. Prior to TGF-β1, dibutyryl-cAMP (dbcAMP), fenoterol, rolipram, cilostamide, and forskolin were used to elevate intracellular cAMP. TGF-β1 induced morphological changes, decreased E-cadherin, but increased collagen Ӏ and cell migration, a process that was reversed by the inhibitor of δ/epsilon casein kinase I, PF-670462. TGF-β1 altered (mRNA, protein) expression of Ezrin, AKAP95, and Yotiao. St-Ht31, the AKAP antagonist, decreased E-cadherin (mRNA, protein), but counteracted TGF-β1-induced collagen Ӏ upregulation. Cigarette smoke (CS) increased TGF-β1 release, activated TGF signaling, augmented cell migration, and reduced E-cadherin expression, a process that was blocked by TGF-β1 neutralizing antibody. The silencing of Ezrin, AKAP95, and Yotiao diminished TGF-β1-induced collagen Ӏ expression, as well as TGF-β1-induced cell migration. Fenoterol, rolipram, and cilostamide, in AKAP silenced cells, pointed to distinct cAMP compartments. We conclude that Ezrin, AKAP95, and Yotiao promote TGF-β1-mediated EMT, linked to a TGF-β1 release by CS. AKAP members might define the ability of fenoterol, rolipram, and cilostamide to modulate the EMT process, and they might represent potential relevant targets in the treatment of COPD.

scholarly journals Targeted DNA oxidation by LSD1–SMAD2/3 primes TGF-β1/ EMT genes for activation or repression

2020 ◽  
Vol 48 (16) ◽  
pp. 8943-8958 ◽  
Author(s):  
Antonio Pezone ◽  
Maria Letizia Taddei ◽  
Alfonso Tramontano ◽  
Jacopo Dolcini ◽  
Francesca Ludovica Boffo ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Dna Oxidation ◽  
Mesenchymal Transition ◽  
Kinase C ◽  
Histone Lysine ◽  
Lysine Specific Demethylase ◽  
Tgf Β1

Abstract The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as a key mediator of EMT in cancer cells, but the precise mechanism that underlies the activation and repression of EMT genes still remains elusive. Here, we characterized the early events induced by TGF-β1 during EMT initiation and establishment. TGF-β1 triggered, 30–90 min post-treatment, a nuclear oxidative wave throughout the genome, documented by confocal microscopy and mass spectrometry, mediated by LSD1. LSD1 was recruited with phosphorylated SMAD2/3 to the promoters of prototypic genes activated and repressed by TGF-β1. After 90 min, phospho-SMAD2/3 downregulation reduced the complex and LSD1 was then recruited with the newly synthesized SNAI1 and repressors, NCoR1 and HDAC3, to the promoters of TGF-β1-repressed genes such as the Wnt soluble inhibitor factor 1 gene (WIF1), a change that induced a late oxidative burst. However, TGF-β1 early (90 min) repression of transcription also required synchronous signaling by reactive oxygen species and the stress-activated kinase c-Jun N-terminal kinase. These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF-β1-induced and -repressed genes involved in the EMT.

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