Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Mennatalla, B.
Role of sclerostin in pulmonary vascular remodelling
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2024. pp.74.
- Autor*innen der Med Uni Graz:
- Biasin Valentina
- Betreuer*innen:
- Biasin Valentina
- Zabini-Polzer Diana
- Altmetrics:
- Abstract:
- a protective effect within the pulmonary endothelial cells, it antagonizes the Wnt/β-catenin pathway, which has been shown to be involved in PAH develop-ment. Additionally, sclerostin improves the endothelial features that are altered as a consequence of PAH progression such as nitric oxide (NO) production and barrier integrity via its inhibitory effect on Src/PYK-2 pathway. Moreover, sclerostin influences the endothelial metabolism dependent on Adenosine monophosphate (AMP)-activated protein kinase (AMPK) expression. It enhances expres-sion of genes involve glucose uptake and glycolysis rate within hPAECs. The expression of lipogen-esis and lipolysis genes show a significant increase upon sclerostin stimulation. In order to further understand if sclerostin enhances lipogenesis or lipolysis, enzyme activity assays should be imple-mented. In order to investigate the molecular mechanisms underlying its protective effect, we took advantage of an unbiased approach such as the kinase array. Hence, we screened several kinases in order to understand which molecular pathway is preferentially activated by sclerostin and we con-firmed these results by western blot on sclerostin stimulated hPAECs. To note, sclerostin shows anti-proliferative effect via its inhibitory action on mTOR and STAT signaling, which could be a novel therapy against altered proliferation, which is one of the main features of endothelial dysfunction in PAH. In conclusion, sclerostin seems to be a promising mediator that could improve many endothelial features within the pulmonary vasculature. Therefore, more efforts should be exerted in order to investigate the role of sclerostin within the pulmonary vasculature and its crosstalk with different cellular pathways.