Object
Title: The role of WNT protein in pathophysiology of cardiac fibrosis
Abstract:
Myocardial fibrosis is a progressive heart disease leading to an abnormal heart structure, which could cause heart failure. Transforming growth factors β (TGF-β) is traditionally considered as a master regulator of the profibrotic processes. WNT signalling pathways have also been found to be implicated in the development of myocardial fibrosis. However, little is known about the interactions of WNT proteins with TGF-β in the pathophysiology of heart fibrosis. The study presented in this dissertation aimed to determine the role of extracellular proteins WNT3a and WNT5a in cardiac fibrosis. After binding to receptor complexes, WNTs trigger various outputs in β- catenin dependent and β-catenin independent manners. In the first phase of the study results showed that WNT proteins transported by exosomes activated WNT pathways in cardiac fibroblasts and this can represent a novel mechanism of spreading profibrotic signals in the heart. Study reveals that in the absence of TGF-β, neither WNT3a nor WNT5a exerted profibrotic responses. However, in contrast to WNT5a, co-stimulation with WNT3a or CHIR – a pharmacological activator of canonical WNT pathway and TGF-β enhanced cardiac fibrosis. Furthermore, in TGF-β-activated fibroblasts, WNT3a stimulated production and secretion of interleukin 11 (IL-11). Neutralization of IL-11 activity with the blocking anti-IL-11 anti ; body effectively reduced the profibrotic response of cardiac fibroblasts activated with TGF-β and WNT3a. In conclusion, WNT/β-catenin signalling promotes TGF-β-mediated fibrogenesis by enhancing IL-11 production.
Place of publishing:
Level of degree:
Degree grantor:
Promoter:
Date issued:
Identifier:
Call number:
Language:
Access rights:
Object collections:
Last modified:
Mar 30, 2023
In our library since:
Jan 25, 2023
Number of object content hits:
0
Number of object content views in PDF format
0
All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/4935
Show description in RDF format:
Show description in OAI-PMH format:
| Edition name | Date |
|---|---|
| ZB-136062 | Mar 30, 2023 |
Objects
Similar
Wójcik-Pszczoła, Katarzyna
