Thesis supervisor: Zoltán Varga
Location of studies (in Hungarian): Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen Abbreviation of location of studies: DEBSI
Description of the research topic:
Vascular smooth muscle cells (VSMC) make up the majority of the normal blood vessel wall giving it structure and regulating its diameter by contracting and relaxing. Following vascular injury, as in atherosclerosis, a switch from the contractile to a synthetic, migratory and proliferative phenotype occurs for tissue repair. If these VSMC fail to switch back to the contractile phenotype due to constant inflammatory signals, they induce pathogenic vascular remodeling and contribute to the formation of atheromatous plaques by secreting calcified matrix components. This reduces the lumen of the artery and makes its walls thicker and stiffer leading to cardiovascular catastrophes.
The voltage-gated proton channel Hv1 conducts protons out of the cell when the intracellular pH drops. It is present in many cell types and is involved in a variety of cellular functions by regulating pH. We have previously found that Hv1 has a role in the differentiation of mesenchymal stem cells in the osteoblast direction, and our preliminary results also indicate the presence of Hv1 in a human aortic SMC line. The aim of our study is to confirm this finding and explore the role of Hv1 in the survival, differentiation and matrix production of VSMC. Using Hv1 inhibitors and gene silencing we will investigate the role of Hv1 in the pH regulation, viability, differentiation into osteoblast-like cells, mineralized matrix production and migration of VSMC in a cell line and also on cells from human samples. By learning the detailed function of Hv1 in VSMC signaling it may become a pharmacological target to interfere with the pathological activity of VSMC in atherosclerosis.
Required language skills: angol középfok Number of students who can be accepted: 2
Deadline for application: 2021-01-16
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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