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

- Autophagy plays important role in the recovery (MET) of mesothelial cells.
- Autophagy is synchronized by various signalling events.
- TGF-β and other cytokines can effect on autophagy.
- Arresting or accelerating autophagy depends on the expression of p-Akt, p-mTOR.
- The cytokine receptor internalization results in an accelerating autophagy.

In previous studies we showed that during Freund's adjuvant induced inflammation rat mesenteric mesothelial cells undergo epithelial-mesenchymal transition type II (EMT). This process was characterized by a dramatic increase of the number of cell organelles and volume of mesothelial cells. After the inflammation reached its maximum, the mesenchymal-like cells gradually regained their epithelial phenotype (mesenchymal-epithelial transition, MET). During the recovery process, the decrease of the number of cell organelles was accompanied by an increasing number of autophagic structures in the cytoplasm, indicating that autophagy might play crucial role in MET. Morphometric data of this study showed that the number of the autophagic organelles increased by the time of inflammation and was the highest at day 7-8, when regeneration started. These morphological observations were supported by immunocytochemistry and Western blot analyses with various markers, directly or indirectly involved in this process. Endocytic markers were expressed at high level during both EMT and MET, while the expression of factors regulating autophagy simultaneously changed with the morphology: p-Akt and p-mTOR level was high at day 3-5 and significantly decreased when autophagy speeded up. The Beclin-1, which is the key factor of initiating autophagy, was expressed at the early time of inflammation. These results strongly suggest that autophagy plays important role in regeneration (MET), and it is regulated and synchronized by various signalling events during inflammation.