Inflammation-Induced Epithelial-to-Mesenchymal Transition and GM-CSF Treatment Stimulate Mesenteric Mesothelial Cells to Transdifferentiate into Macrophages
| Autor: | Nikolett Dóczi, Viktória Zsiros, Sándor Katz, Anna L. Kiss |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition MAP Kinase Signaling System media_common.quotation_subject Immunology Immunocytochemistry Caveolin 1 Inflammation 03 medical and health sciences Peritoneal cavity Western blot medicine Immunology and Allergy Animals Mesentery Epithelial–mesenchymal transition Internalization media_common Early Growth Response Protein 1 030102 biochemistry & molecular biology medicine.diagnostic_test Chemistry Tumor Necrosis Factor-alpha Macrophages Granulocyte-Macrophage Colony-Stimulating Factor Epithelial Cells Cell biology Rats 030104 developmental biology medicine.anatomical_structure Cell Transdifferentiation Tumor necrosis factor alpha medicine.symptom Mesothelial Cell Signal Transduction |
| Zdroj: | Inflammation. 41(5) |
| ISSN: | 1573-2576 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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