Date of Award

12-16-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Hamed Laroui

Second Advisor

Kathryn Grant

Third Advisor

Donald Hamelberg

Abstract

CD98 is a multifunctional glycoprotein that is involved in various biological processes such as amino acid transport and cell adhesion, diffusion, and proliferation. Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. The role of CD98 in NAFLD has not thoroughly been examined and there are limited reports in the literature with regards CD98 relation to liver disease. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) and plant derived nanovesicles could attenuate liver disease markers in a mouse model of NAFLD. The nanoparticles strongly decreased all markers of NAFLD, including the blood levels of ALT and lipids accumulation, fibrosis evidence and pro-inflammatory cytokines. Treatment with the plant nanovesicles attenuated inflammation and steatosis in the mouse NAFLD model. In conclusion, our results indicate that CD98 appears to function as a key actor/inducer in NAFLD, and that our NPs approach may offer a new targeted therapeutic for this disease.

Exosomes are nanovesicles that are secreted by cells and participate in intercellular communication via exchange of cargo such as oligonucleotides, lipids, proteins, and peptides. Lately the role of tumor derived exosomes has been questioned for aiding metastasis as some tumor derived exosomes participate in developing cellular environments that support metastasis in various organs. Patients suffering from colorectal cancer commonly develop liver metastasis, thus the role of exosomes from colorectal cancer could participate in the development of metastasis in the liver. Our results demonstrated that exosomes derived from Caco2 BBe can increase integrin signaling which can contribute to metastasis or more tumorigenic phenotype.

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