Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis

“…Ma L et.al reported that MSC-derived exosomes loaded with therapeutic circRNAs-circDIDO1 suppressed HSC activation in liver fibrosis [ 49 ]. In another study, researchers utilized plasma-derived exosomes containing FZD receptor protein (FZD7) to modulate the dysregulated Wnt/Frizzled (FZD) signaling in nonalcoholic fatty liver disease (NAFLD) [ 50 ]. These studies unveiled that different kinds of exosomes are natural nanoparticles for rescuing liver injury.…”

The multiple combination of Paclitaxel, Ramucirumab and Elacridar reverses the paclitaxel-mediated resistance in gastric cancer cell lines

“…Medium derived from both HGC27-R and KATOIII-R was processed for exosome isolation, in according to a previously published procedure ( 27 ) and as reported in the MISEV 2018 guidelines ( 28 ). Briefly, the culture medium of cells was centrifuged for 10 minutes at 1500× g (Thermo Scientific, Heraeus Multifuge X3 Centrifuge).…”

“…The pellet consisting of purified exosomes was recovered and dispersed in 200 μL of ultrapure water for the chemical-physical characterization and protein extraction or in sterile PBS for the cultured cell. After the exosome extraction, a characterization of freshly isolated exosome samples was performed by Dynamic Light Scattering (DLS) analysis, ς-Potential measurements and Transmission Electron Microscopy (TEM) investigation as previously reported ( 27 ). The remaining sample was stored at -80°C until protein extraction was assessed.…”

Emerging role of engineered exosomes in nonalcoholic fatty liver disease

“…Furthermore, microarray analysis of exosomal miRNAs isolated from the serum of 41 patients with NAFLD (diagnosed using liver biopsy) suggested that serum exosomal miRNAs could be used to assess the severity of NAFLD and identify potential targets for NAFLD treatment[ 33 ]. One of the determinants of liver degeneration in the progression of NAFLD is Wnt/frizzled (FZD) signalling; for example, FZD7 delivered by plasma-derived exosomes is a good candidate for a novel and effective biomarker for the diagnosis and prognosis of NAFLD[ 51 ].…”