Autophagy is the key process in the re-establishment of the epitheloid phenotype during mesenchymal-epithelial transition (MET)

Zsiros, Viktória; Katz, Sándor; Dóczi, Nikolett; Kiss, Anna L.

doi:10.1016/j.yexcr.2017.02.031

Cited by 9 publications

(29 citation statements)

References 49 publications

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“…Recent studies show that autophagycan play an essential role in inflammatory processes as well [18,19]. At the start and subsequent development of regeneration a progressive autophagosome and autolysosome formation were found in our system [20]. Simultaneously with the morphological changes, the expression of various factors directly or indirectly regulating autophagy has also changed.…”

Section: During Recovery Mesothelial Cells Undergo Mesenchymal-mentioning

confidence: 52%

“…When theTGFβ receptor is internalized, the ligand cannot transmit the stimulus to the downstream molecules, and EMT is blocked. In our system, it also means that by the receptor internalizationthe inhibitory effect of the downstream signalling is stopped, mTOR can initiate autophagy, and the recovery (MET) can start [20].From these data, we conclude that the receptor internalization can be one of the most important steps in allowing autophagy through inactivation of PI3K-Akt-mTOR pathway as well. Summarizing: caveolae, the omega-shaped plasma membrane invaginations, have multiple functions in signalling events.…”

Section: Essential Role Of Caveolae and Caveolar Endocytosis In Ementioning

confidence: 53%

“…Since in our system TGF-β is secreted into the peritoneal cavity during inflammation [13,28], we assume that TGF-β not only stimulates the EMT (through its canonical pathway), but it also arrests the autophagy by stimulating the phosphorylation of Akt-mTOR.When the inflammation progressed and the autophagy was arrested we found high p-Akt and p-mTOR levels. Following the peak time of inflammationboth p-Akt and p-mTOR levels diminished and the number of autophagic vacuoles increased significantly, indicating that simultaneously with the inactivationof regulatory molecules the autophagy could be accelerated [20]. These results show thatduring inflammation TGF-β has a dual effect: through its plasma membrane receptor, it stimulates EMT (canonic pathway) andby stimulating PI3K-Akt pathway, indirectly inhibits autophagy.…”

Section: During Recovery Mesothelial Cells Undergo Mesenchymal-mentioning

confidence: 78%

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Inflammatory Cytokinesinduce EMT in Mesenteric Mesothelial Cells, and Transdifferentiate Them into Macrophages

Kiss¹

2018

World Journal of Research and Review

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Section: During Recovery Mesothelial Cells Undergo Mesenchymal-mentioning

confidence: 52%

Section: Essential Role Of Caveolae and Caveolar Endocytosis In Ementioning

confidence: 53%

Section: During Recovery Mesothelial Cells Undergo Mesenchymal-mentioning

confidence: 78%

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Inflammatory Cytokinesinduce EMT in Mesenteric Mesothelial Cells, and Transdifferentiate Them into Macrophages

Kiss¹

2018

World Journal of Research and Review

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“…After the peak time of inflammation the GM-CSFR β was present in late endosomes, proving that it has been transported to the degradative pathway. As the receptor degraded, EMT became gradually diminished and the regeneration (mesenchymal-epithelial transition, MET) started, the mesothelial cells gradually regained their simple squamous epithelial morphology and cellular organization [35]. The cells, being still cuboidal in shape, arranged in a single layer on the surface of the mesentery, the volume of the cytoplasm gradually decreased, and finally only few intracellular organelles were present in the cytoplasm [35].…”

Section: Autophagy Plays Important Role In Regeneration the Mesenchymentioning

confidence: 99%

Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells

Zsiros

Kiss

2020

Inflamm. Res.

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In this review we summarize the cellular and molecular events of inflammation induced epithelial-to-mesenchymal (EMT) and mesothelial-to-macrophage transition (MET) during regeneration. Since the receptor transmits the environmental stimulus, downregulating or upregulating the process on an epigenetic level, the intracellular localization of receptors (signaling organelles: early endosomes or lysosomal degradation: late endosomes) plays a crucial role in the signaling events regulating inflammation and regeneration. Therefore, we focused on the internalization of the receptors as well as the intracellular compartmentalization of signaling molecules during EMT and MET. The review draws the reader’s attention to the plasticity of mesothelial cells and supports the idea that during inflammation an ambient macrophage population might derive from mesothelial cells.

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“…by supressing the E-cadherin gene expression [24] and 2.) arresting autophagy [25]. When TGFβ receptor is internalized via caveolae, the TGFβ signal is not transmitted to PI3K-Akt pathway, mTOR is not phosphorylated, it can accelerate autophagy, and E-cadherin can be synthesized.…”

mentioning

confidence: 99%

Caveolin-1/Caveolae are in Focus of Regulating EMT and MET

Kiss¹

2017

Histol Cytol Embryol

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During epithelial-mesenchymal transition (EMT) polarized epithelial cells undergo a complex proteomic remodelling, several biochemical and morphological changes converting them into mesenchymal-like cells. [1]. Besides of expressing mesenchymal markers (N-cadherin, vimentin, α-smooth muscle actin etc) they acquire the ability to produce extracellular matrix components, as well as metalloproteinases, inflammatorycytokines, fibrogenic and angiogenic factors [2]. Three types of EMTs have been distinguished so far: epithelial-mesenchymal transition during embryogenesis (type I), EMT associated with inflammation, wound healing, tissue regeneration and organ fibrosis (type II) and tumorigenesis (type III) [3]. EMT is triggered by extracellular signals including various cytokines, growth factors, extracellular matrix components. Transforming growth factorβ (TGFβ) family members are the most important regulators in this process. The TGFβ signalling pathways are generally divided into Smad-dependent and Smad-independent processes. When TGFβ binds to its primary serine/threonine kinase receptor (type II) it induces the formation of a heteroterameric receptor complex. Type II receptor thentrans phosphorylates (activates) the signalling receptor (type I) that can initiate Smad2/3 signalling pathway. The receptor internalization is required for the initiation of downstream signalling [4]. In addition to promoting the signalling process by transporting these molecules to the signalling organelles, the receptor-ligand internalization can control the number of receptors present on the cell surface. Thus, receptor internalization regulates the signalling, receptor turnover, the magnitude and duration of the events. In EMT clathrinmediated as well as caveolar endocytosis (internalization via caveolae) play an important role [5]. Caveolae are small omega-or flask-shaped plasma membrane invaginations, highly hydrophobic membrane domains (lipid rafts) containing a special protein, caveolin-1 [6,7]. It is generally accepted that endocytosis via caveolae directs the receptorligand complex to lysosomal and/or proteasomal degradation [8,9] which downregulates the receptors on the cell surface. Caveolin-1 downregulation together with caveolar internalization of TGFβ receptorsturns off the TGFβ signalling pathway,thereby blocking EMT.TGFβ can induce and/or promote EMT through a Smadindependent pathway as well. In response to TGFβ the type II TGFβ receptor can autophosphorylate tyrosine amino acids (Tyr259, 336 and 424) [10], and can undergo Src-mediated tyrosine phosphorylation as well [11,12]. Thetyrosine phosphorylated TGFβ receptor can activate MAP kinase (MEK) and ERK1/2. Members of the Ras/Raf/MEK/ ERK kinase cascades are present in caveolae and caveolin-1 promotes ERK activation. Kinase suppressor of Ras1 (KSR1) is a caveolin-1 interacting protein, and the KSR1-caveolin-1 interaction is required for the redistribution of MEK/ERK in caveolin-rich fractions, actually caveolin-1 facilitates the formation of KSR1/MEK/ERK complex.KSR1-...

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Autophagy is the key process in the re-establishment of the epitheloid phenotype during mesenchymal-epithelial transition (MET)

Cited by 9 publications

References 49 publications

Inflammatory Cytokinesinduce EMT in Mesenteric Mesothelial Cells, and Transdifferentiate Them into Macrophages

Inflammatory Cytokinesinduce EMT in Mesenteric Mesothelial Cells, and Transdifferentiate Them into Macrophages

Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells

Caveolin-1/Caveolae are in Focus of Regulating EMT and MET

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