EMT induced by EGF and wounding activates hyaluronan synthesis machinery and EV shedding in rat primary mesothelial cells
| Autor: | Kirsi Rilla, Kai Härkönen, Uma Thanigai Arasu, Riikka Kärnä, Ville Koistinen, Sanna Oikari |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Epithelial-Mesenchymal Transition Primary Cell Culture Apoptosis Biology Epithelium Extracellular Vesicles 03 medical and health sciences 0302 clinical medicine medicine Animals Epithelial–mesenchymal transition Hyaluronic Acid Rats Wistar Cell Shape Molecular Biology Wound Healing Epidermal Growth Factor integumentary system Caspase 3 Epithelial Cells Extracellular vesicle Hyaluronan-mediated motility receptor Cell biology Mesothelium Hyaluronan Receptors 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Wound healing Filopodia Mesothelial Cell |
| Zdroj: | Matrix Biology. 63:38-54 |
| ISSN: | 0945-053X |
| DOI: | 10.1016/j.matbio.2016.12.007 |
| Popis: | The mesothelium is a membrane that forms the lining of several body cavities. It is composed of simple squamous mesothelial cells that secrete a glycosaminoglycan-rich lubricating fluid between inner organs. One of the most abundant glycosaminoglycans of those fluids is hyaluronan, which is synthesized on a plasma membrane and especially on apical filopodia of cultured cells. Our recent study showed that similar hyaluronan-rich protrusions are found in mesothelial lining in vivo, which suggests that hyaluronan synthesis in plasma membrane protrusions is a general process. However, the mesothelial lining was negative for the hyaluronan receptor CD44 while in many previous studies cultured mesothelial cells have been shown to express CD44. To further explore these findings we induced epithelial to mesenchymal transition in primary rat mesothelial cells by EGF-treatment and scratch wounding. Surprisingly, the results showed that at a normal epithelial, confluent stage the mesothelial cells are negative for CD44, but EMT induced by EGF or wounding activates CD44 expression and the whole hyaluronan synthesis machinery. In addition to typical EMT-like morphological changes, the growth of apical filopodia and budding of extracellular vesicles (EVs) were induced. In summary, the results of this study show that the activation of hyaluronan synthesis machinery, especially the expression of CD44 is strongly associated with EMT induced by EGF and wounding in mesothelial cells. Moreover, EMT enhances the secretion of EVs that carry CD44 and hyaluronan, which may be important regulators in EV interactions with their targets and ECM remodeling. The results of the present study also suggest that CD44 is a potential marker for EVs, especially those secreted from cells during tissue repair and pathological processes. |
| Databáze: | OpenAIRE |
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