Granty a projekty

Vliv Carotuximabu na expresi a signalizaci endoglinu a hladiny solubilního endoglinu během jaterního poškození

Endoglin is a transmembrane glycoprotein existing in two forms, namely membrane endoglin (Eng) and soluble endoglin (sEng) circulating in the blood. It has been demonstrated that Eng might support the process of fibrosis, affect inflammation, and endothelial dysfunction in various organs. In addition, sEng levels were increased in liver diseases suggesting sEng might represent a potential biomarker of liver injury, including fibrosis and/or nonalcoholic steatohepatitis (NASH). However, the precise role of Eng expression, signaling, and sEng levels during these pathological changes in the liver are unknown. Carotuximab (TRC105) is a human/murine therapeutic monoclonal antibody that binds murine Eng and affects Eng expression, signaling, and sEng levels. We hypothesize that Carotuximab prevents liver alteration by modulating Eng and sEng in experimental liver fibrosis and inflammation. We will try to elucidate Carotuximab treatment's impact in carbon tetrachloride-induced mouse model of liver fibrosis and diet-induced NASH experimental mouse model. We will focus on analysis of lipids, sEng levels, liver histology, qRT-PCR, immunohistochemistry and Western blot (Eng, Smad2/3, Smad1/5, markers of endothelial cells, hepatic stellate cell, inflammation, liver fibrosis. This grant proposal should help us elucidate whether Carotuximab can affect liver alteration and function in proposed pathological experimental conditions by modulating Eng expression and signaling and sEng levels.

Číslo: GAUK362221

Období: 01.01.2021 - 31.12.2023

Poskytovatel: Univerzita Karlova - Grantová agentura UK

Hlavní řešitel: Eissazadeh Samira - Farmaceutická fakulta v Hradci Králové

Celkový objem financí: 594 000,00 Kč

Interní řešitelé

Hlavní řešitel: Samira Eissazadeh - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Ivone Cristina Igreja e Sá, M.Sc. - Farmaceutická fakulta v Hradci Králové, FaF HK
Školitel: prof. PharmDr. Petr Nachtigal, Ph.D. - Univerzita Karlova,

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