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Inflammation-Induced Epithelial-to-Mesenchymal Transition and GM-CSF Treatment Stimulate Mesenteric Mesothelial Cells to Transdifferentiate into Macrophages

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Abstract

In our previous work, we showed that during inflammation-induced epithelial-to-mesenchymal transition (EMT), mesenteric mesothelial cells express ED1 (pan-macrophage marker), indicating that they are transformed into macrophage-like cells. In this paper, we provide additional evidences about this transition by following the phagocytic activity and the TNFα production of mesenteric mesothelial cells during inflammation. Upon injection of India ink particles or fluorescent-labeled bioparticles (pHrodo) into the peritoneal cavity of rats pretreated with Freund‘s adjuvant, we found that mesothelial cells efficiently engulfed these particles. A similar increase of internalization could be observed by mesothelial cells in GM-CSF pretreated primary mesenteric culture. Since macrophages are the major producers of tumor necrosis factor, TNFα, we investigated expression level of TNFα during inflammation-induced EMT and found that TNFα was indeed expressed in these cells, reaching the highest level at the 5th day of inflammation. Since TNFα is one of the target genes of early growth response (EGR1) transcription factor, playing important role in monocyte-macrophage differentiation, expression of EGR1 in mesothelial cells was also investigated by Western blot and immunocytochemistry. While mesothelial cells did not express EGR1, a marked increase was observed in mesothelial cells by the time of inflammation. Parallel to this, nuclear translocation of EGR1 was shown by immunocytochemistry at the day 5 of inflammation. Caveolin-1 level was high and ERK1/2 became phosphorylated as the inflammation proceeded showing a slight decrease when the regeneration started. Our present data support the idea that under special stimuli, mesenteric mesothelial cells are able to transdifferentiate into macrophages, and this transition is regulated by the caveolin-1/ERK1/2/EGR1 signaling pathway.

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Acknowledgements

We would like to express our thankfulness to Professor Pál Röhlich for the precious comments and accurate language correction of the manuscript. Special thanks are due to Katalin Lőcsey for her valuable technical help.

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Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Semmelweis University, Tűzoltó u. 58, Budapest, 1094, Hungary

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

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  1. Sándor Katz
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  2. Viktória Zsiros
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  3. Nikolett Dóczi
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  4. Anna L. Kiss
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Correspondence to Anna L. Kiss.

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Katz, S., Zsiros, V., Dóczi, N. et al. Inflammation-Induced Epithelial-to-Mesenchymal Transition and GM-CSF Treatment Stimulate Mesenteric Mesothelial Cells to Transdifferentiate into Macrophages. Inflammation 41, 1825–1834 (2018). https://doi.org/10.1007/s10753-018-0825-4

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