Investigation of Angiotensin II-induced Gene Expression Changes in Vascular Smooth Muscle Cells
Gém Janka Borbála
Molecular Medicine Division
Dr. Várnai Péter
SE EOK Szent-Györgyi Albert előadóterem
2026-07-09 13:00:00
Cellular and Molecular Physiology
Dr. Hunyady László
Dr. Balla András és Dr. Hunyady László
Dr. Dézsi László
Dr. Fagyas Miklós
Dr. Rónai Zsolt
Dr. Kardon Tamás
Dr. Boratkó Anita
During my PhD work, my research mainly focused on the AngII provoked long term effects in the vascular smooth muscle cells.
Using Affymetrix gene-chip assay, we identified numerous genes, up- or downregulated in VSMCs to AngII stimuli. Firstly, we focused on LMCD1, the gene of a LIM-protein, basically regulating proliferative cellular functions as a transcriptional co-factor. We investigated the main signal transduction pathways that lead to LMCD1 upregulation in VSMCs to AngII treatment. Furthermore, we described the effects of LMCD1 protein overexpression on cellular proliferation and migration.
Due to the results of PROGENy pathway analysis, we evaluated the importance of AT1R dependent EGFR transactivation in VSMCs. We evaluated the importance of AT1R activation related EGFR transactivation in the case of the genes of three different dual specificity phosphatase isoforms, which were proved to be significantly upregulated by AngII in VSMCs. Our findings demonstrate that genetic silencing of EGFR did not cause such a spectacular reduction of AngII induced upregulation in the case of DUSP5, DUSP6 and DUSP10 genes, than we could measure using pharmacological inhibition of EGFR protein. Since pharmacological inhibitors often inhibit off-target proteins too, it is possible that there are other tyrosine-kinases that play an important role in the AngII-mediated upregulation of the three examined genes. Based on our yet unpublished data, we found proof that dasatinib sensitive tyrosine-kinases, like Src family kinases, might be responsible in this process, but the examination and description of the exact pathways leading to AngII mediated upregulation of DUSP5, DUSP6 and DUSP10 genes will have to be the subject of our future research.
