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| Author(s): |
Bruna de Araujo Cardoso dos Santos
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2021-07-02 |
| Examining board members: |
Alice Cristina Rodrigues;
Eliana Hiromi Akamine;
Ana Carolina Migliorini Figueira;
Adriana Souza Torsoni
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| Advisor: | Alice Cristina Rodrigues; Emer Suavinho Ferro |
| Abstract | |
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of diseases ranging from the presence of hepatic steatosis (accumulation of fat in the liver parenchyma without inflammation) in the absence of excessive alcohol consumption to steatohepatitis, characterized by steatosis along with hypertrophy of the hepatocyte and lobular inflammation, which may progress, in the long term, to fibrosis, cirrhosis and hepatocellular carcinoma. Mouse knockout for an enzyme thimet oligopeptidase (THOP-/-) is resistant to the induction of obesity and NAFLD by a high-fat diet, and shows changes in the expression of microRNAs previously associated with NAFLD. In order to clarify how the THOP1 deletion protects the animal from developing steatohepatitis and how this mechanism can be associated with microRNAS, we used C57Bl/6 wild type and THOP-/- animals fed a choline-deficient and hyperlipidic diet, which better mimics the evolution of the disease, for 8, 15 and 24 weeks. After the experimentation period, the animals were euthanized and the liver was collected for analysis of liver histology and metabolic pathways through gene expression by qPCR. The results obtained indicate that, in the long term, the THOP-/- genotype promotes a phenotype resistant to obesity, steatohepatitis and fibrosis. This improvement in the phenotype is related to the downregulation of miR-34a and the metabolic and inflammatory pathways that involves Pparg, Ucp2, Tnfa, IL-6, IL-10, IL-17, Tgfb, a-sma, Col1a1 and Timp1. The decrease in these pathways seems to be related to the accumulation of VDPVNFK, over time, which can modulate the expression of miR-34a, thus inhibiting the action of this microRNA and allowing the signaling pathways to work to decrease lipid accumulation and its consequences. (AU) | |
| FAPESP's process: | 19/15965-8 - Regulation of the expression of microRNAs by intracellular peptides in the induction of non-alcoholic steatohepatitis in knockout mice for EP24.15 |
| Grantee: | Bruna de Araújo Cardoso dos Santos |
| Support Opportunities: | Scholarships in Brazil - Master |