Sejt- és Molekuláris Biológiai Laboratórium / Laboratory of Cell and Molecular Biology

Head of the lab:

•  Dr. L. Kiss, Anna, Ph.D., D.Sc., full professor

Staff:

• Dr. Katz, Sándor, assistant professor
• Dr. Horváth, András, assistant professor
• Zsiros, Viktória, lecturer
• Szemere, Lászlóné, technician
• Dóczi, Nikolett, technician

In our Laboratory we have been studying the epithelial-to-mesenchymal transition (EMT) which is a complex biological process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype. EMT or transdifferentiation is involved in a variety of normal physiological, as well as pathological processes such as development, metastatic potential in malignancy and inflammation. We have previously demonstrated that peritoneal injection of Freund’s adjuvant induces inflammation, accompanied by an extensive cellular proliferation, migration, structural reorganization as well. The inflammatory process reaches the maximum level (day 5-8), and then the regeneration, the mesenchymal-epithelial transition (MET) starts, when the mesothelial cells gradually regain their original simple squamous epithelial character, their synthetic and metabolic activities are significantly decreasing, they remove the excess of cellular organelles by autophagy. In contrast to EMT, less is known about the steps and regulation of MET, how the autophagy is synchronized with EMT and MET, which cellular/cytoplasmic compartments give place to the molecules taking part in the downstream events of the regulation and how the localization of these proteins changes during inflammation and the regeneration. Our main goal is to clarify the significance of endocytosis and the role of caveolae/caveolin isoforms in the signalling events and the regulation of the process.

Our research tries to answer basic cell biological questions.

• To clarify the role of endocytosis, especially the caveola-mediated endocytosis in the signalling processes during MET and mesothel-macrophage transition, to find out that early endosomes are the key signalling organelles in EMT and MET. To clarify the role of multivesicular bodies, the important intermediate organelles in turning off process, by degrading the molecules involved in EMT and/or MET.
• To study the steps and regulation of mesothel-macrophage transdifferentiation. To follow the signalling pathway, to clarify the role of endocytosis (especially the caveola-mediated one) in the signalling processes. To provide more evidences about that mesenteric mesothelial cells are not finally differentiated cells, they seem to be easy to differentiate into other special cells, thus they can be taken as a special kind of “stem” cells. To understand the regulation of this transdifferentiation provides chances for clinical application.
• Our project can help to answer clinical questions as well. The application of continuous ambulatory peritoneal dialysis (CAPD) induces epithelial-mesenchymal transition in mesothelial cells. Soon after dialysis is initiated, peritoneal mesothelial cells undergo a transition from epithelial to mesenchymal phenotype. Thus mesothelial cells are sources of mesenchymal cells during inflammation and tissue regeneration, they can play important role during the adhesive and fibrotic events of the serosa. During inflammation the mesothelial cells are becoming free-floating cells, these free-floating cells move down chemotactic gradients, attach to extracellular matrix components or they are deposited from the serosal fluid, then proliferate and reconstitute an intact mesothelial monolayer.

Techiques: Immunocytochemistry on semithin and ultrathin frozen sections, light-and confocal microscopy, electron microscopical techniques, cell culturing, Western blot, morphometry, cell fractioning