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Inflammation Research
Published in: Inflammation Research 12/2020

01-12-2020 | Cytokines | Review

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

Authors: Viktória Zsiros, Anna L. Kiss

Published in: Inflammation Research | Issue 12/2020

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Abstract

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.
Literature
1.
Katz S, Balogh P, Kiss AL. Mesothelial cells can detach from the mesentery and differentiate into macrophage-like cells. APMIS. 2011;119:782–93.PubMedCrossRef
2.
Savagner P. Leaving the neighborhood: molecular mechanisms involved during epithelial–mesenchymal transition. BioEssays. 2001;23:912–23.PubMedCrossRef
3.
Boyer B, Vallés AM, Edme N. Induction and regulation of epithelial–mesenchymal transitions. Biochem Pharmacol. 2000;60:1091–9.PubMedCrossRef
4.
Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol. 2001;159:1465–75.PubMedPubMedCentralCrossRef
5.
Strippoli R, Loureiro J, Moreno V, Benedicto I, Pérez Lozano ML, Barreiro O, et al. Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial–mesenchymal transition and fibrosis during peritoneal dialysis. EMBO Mol Med. 2015;7:102–23.PubMedCrossRef
6.
7.
Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172:973–81.PubMedPubMedCentralCrossRef
8.
9.
Zavadil J, Böttinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005;24:5764–74.PubMedCrossRef
10.
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–84.PubMedCrossRef
11.
Hayes S, Chawla A, Corvera S. TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol. 2002;158:1239–49.PubMedPubMedCentralCrossRef
12.
Balogh P, Katz S, Kiss AL. The role of endocytic pathways in TGF-β signaling. Pathol Oncol Res. 2013;19:141–8.PubMedCrossRef
13.
Katz S, Balogh P, Nagy N, Kiss AL. Epithelial-to-mesenchymal transition induced by Freund’s adjuvant treatment in rat mesothelial cells: a morphological and immunocytochemical study. Pathol Oncol Res. 2012;18:641–9.PubMedCrossRef
14.
Katz S, Zsiros V, Dóczi N, Szabó A, Biczó Á, Kiss AL. GM-CSF and GM-CSF receptor have regulatory role in transforming rat mesenteric mesothelial cells into macrophage-like cells. Inflamm Res. 2016;65:827–36.PubMedCrossRef
15.
Kiss AL, Kittel A. Early endocytotic steps in elicited macrophages: omega-shaped plasma membrane vesicles at their cell surface. Cell Biol Int. 1995;19:527–38.PubMedCrossRef
16.
Kiss AL, Turi ATA, Müller N, Kántor O, Botos E. Caveolae and caveolin isoforms in rat peritoneal macrophages. Micron. 2002;33:75–93.PubMedCrossRef
17.
18.
Wiese C, Rolletschek A, Kania G, Blyszczuk P, Tarasov KV, Tarasova Y, et al. Nestin expression—a property of multi-lineage progenitor cells? Cell Mol Life Sci. 2004;61:2510–22.PubMedCrossRef
19.
20.
Katz S, Zsiros V, Dóczi N, Kiss AL. Inflammation-induced epithelial-to-mesenchymal transition and GM-CSF treatment stimulate mesenteric mesothelial cells to transdifferentiate into macrophages. Inflammation. 2018;41:1825–34.PubMedCrossRef
21.
Baron V, Adamson ED, Calogero A, Ragona G, Mercola D. The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther. 2006;13:115–24.PubMedPubMedCentralCrossRef
22.
Laslo P, Spooner CJ, Warmflash A, Lancki DW, Lee H-J, Sciammas R, et al. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell. 2006;126:755–66.PubMedCrossRef
23.
Krishnaraju K, Nguyen HQ, Liebermann DA, Hoffman B. The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells. Mol Cell Biol. 1995;15:5499–507.PubMedPubMedCentralCrossRef
24.
Krishnaraju K, Hoffman B, Liebermann DA. The zinc finger transcription factor Egr-1 activates macrophage differentiation in M1 myeloblastic leukemia cells. Blood. 1998;92:1957–66.PubMedCrossRef
25.
Krishnaraju K, Hoffman B, Liebermann DA. Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages. Blood. 2001;97:1298–305.PubMedCrossRef
26.
Fu Y, Moore X-L, Lee MKS, Fernández-Rojo MA, Parat M-O, Parton RG, et al. Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages. Arterioscler Thromb Vasc Biol. 2012;32:117–25.
27.
Varzaneh FN, Keller B, Unger S, Aghamohammadi A, Warnatz K, Rezaei N. Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic targets—a review of the current knowledge. J Clin Immunol. 2014;34:524–43.PubMedCrossRef
28.
Katz S, Zsiros V, Kiss AL. Under inflammatory stimuli mesenteric mesothelial cells transdifferentiate into macrophages and produce pro-inflammatory cytokine IL-6. Inflamm Res. 2019;68:525–8.PubMedPubMedCentralCrossRef
29.
Taga T, Kishimoto T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol. 1997;15:797–819.PubMedCrossRef
30.
Hansen G, Hercus TR, McClure BJ, Stomski FC, Dottore M, Powell J, et al. The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell. 2008;134:496–507.PubMedCrossRef
31.
Hercus TR, Thomas D, Guthridge MA, Ekert PG, King-Scott J, Parker MW, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood. 2009;114:1289–98.PubMedPubMedCentralCrossRef
32.
Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, et al. Granulocyte–macrophage colony-stimulating factor: not just another haematopoietic growth factor. Med Oncol. 2014;31:774.PubMedCrossRef
33.
Zsiros V, Katz S, Doczi N, Kiss AL. Endocytosis of GM-CSF receptor β is essential for signal transduction regulating mesothelial-macrophage transition. Biochim Biophys Acta Mol Cell Res. 2019;1866:1450–62.PubMedCrossRef
34.
Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T. Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell. 2006;10:839–50.PubMedCrossRef
35.
Zsiros V, Katz S, Dóczi N, Kiss AL. Autophagy is the key process in the re-establishment of the epitheloid phenotype during mesenchymal-epithelial transition (MET). Exp Cell Res. 2017;352:382–92.PubMedCrossRef
36.
Gajewska M, Zielniok K, Motyl T. Autophagy in development and remodelling of mammary gland. Autophagy—a double-edged sword—cell surviv or death? InTech. 2013;2:2.
37.
38.
Periyasamy-Thandavan S, Jiang M, Schoenlein P, Dong Z. Autophagy: molecular machinery, regulation, and implications for renal pathophysiology. Am J Physiol Renal Physiol. 2009;297:F244–F256256.PubMedPubMedCentralCrossRef
39.
Mizushima N. The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ. 2005;12:1535–41.PubMedCrossRef
40.
41.
42.
43.
44.
Codogno P, Meijer AJ. Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ. 2005;2:1509–18.CrossRef
45.
46.
Wang J, Whiteman MW, Lian H, Wang G, Singh A, Huang D, et al. A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1. J Biol Chem. 2009;284:21412–244.PubMedPubMedCentralCrossRef
47.
48.
Balogh P, Magyar M, Szabó A, Müllner N, Likó I, Patócs A, et al. The subcellular compartmentalization of TGFβ-RII and the dynamics of endosomal formation during the signaling events: an in vivo study on rat mesothelial cells. Eur J Cell Biol. 2015;94:204–13.PubMedCrossRef
49.
Wendt MK, Allington TM, Schiemann WP. Mechanisms of the epithelial-mesenchymal transition by TGF-beta. Future Oncol. 2009;5:1145–68.PubMedCrossRef
50.
Lamouille S, Connolly E, Smyth JW, Akhurst RJ, Derynck R. TGF-beta-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. J Cell Sci. 2012;125:1259–73.PubMedPubMedCentralCrossRef
51.
Lamouille S, Derynck R. Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. J Cell Biol. 2007;178:437–51.PubMedPubMedCentralCrossRef
Metadata
Title
Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells
Authors
Viktória Zsiros
Anna L. Kiss
Publication date
01-12-2020
Publisher
Springer International Publishing
Keyword
Cytokines
Published in
Inflammation Research / Issue 12/2020
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-020-01400-7

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