Circulating exosomal microRNAs as potential biomarkers of hepatic injury and inflammation in a murine model of glycogen storage disease type 1a

Abstract

Most patients affected by glycogen storage disease type 1a (GSD1a), an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α), develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma. The purpose of this study was to identify potential biomarkers of the pathophysiology of the GSD1a-affected liver. To this end, we used the plasma exosomes of a murine model of GSD1a, the LS-G6pc−/− mouse, to uncover the modulation in microRNA expression associated with the disease. The microRNAs differentially expressed between LS-G6pc−/− and wild-type mice, LS-G6pc−/− mice with hepatocellular adenoma and LS-G6pc−/− mice without adenoma, and LS-G6pc−/− mice with amyloidosis and LS-G6pc−/− mice without amyloidosis were identified. Pathway analysis demonstrated that the target genes of the differentially expressed microRNA were significantly enriched for the insulin signaling pathway, glucose and lipid metabolism, Wnt/β-catenin, telomere maintenance and hepatocellular carcinoma, and chemokine and immune regulation signaling pathways. Although some microRNAs were common to the different pathologic conditions, others were unique to the cancerous or inflammatory status of the animals. Therefore, the altered expression of several microRNAs is correlated with various pathologic liver states and might help to distinguish them during the progression of the disease and the development of late GSD1a-associated complications.

Exosomal MicroRNAs as Potential Biomarkers of Hepatic Injury and Kidney Disease in Glycogen Storage Disease Type Ia Patients

“…To identify potential biomarkers of the pathophysiology of the GSDIa-affected liver we have recently analyzed the plasma exosomes of a murine model of GSDIa in an LS- G6pc −/− mouse [ 11 ] to uncover the modulation of the microRNA expression associated with the disease [ 12 ], as well as the proteomic expression profile in the liver of the same mouse model [ 60 ].…”

“…This animal model could provide an efficient means of discovering the diagnostic markers of hepatic tumors since the liver is the only organ affected in these mice. The results of that study revealed that the altered expression of several Exo-miRs correlated with various pathologic liver states associated with the progression of the disease, among which Exo-miRs discriminated LS- G6pc −/− mice with adenomas from LS- G6pc −/− mice without adenomas [ 12 ].…”

Diagnostic Potential of Plasma Extracellular Vesicle miR-483-3p and Let-7d-3p for Sepsis

“…We chose to focus on the upregulated miRNAs. It has been reported that 6 out of the 11 upregulated miRNAs, including miR- 483-3p, miR-328-3p, let-7d-3p, miR-92b-5p, miR-381-3p, and miR-210-5p, are involved in injury and inflammation (Lin et al, 2019;Fu et al, 2020;Maemura et al, 2020;Resaz et al, 2020). Subsequently, plasma EVs from the validation cohort of 37 sepsis patients at admission and 25 healthy controls were examined for the expression of the 6 inflammation-related miRNAs via qRT-PCR.…”

Exosomes from mesenchymal stem cells expressing microribonucleic acid-125b inhibit the progression of diabetic nephropathy <i>via</i> the tumour necrosis factor receptor-associated factor 6/Akt axis

“…Wang D et al showed that MSC-Exos targeting miR-125b could inhibit neointimal hyperplasia by activating myosin IE [10]. Moreover, the function of exosomes in cells provides multiple therapeutic applications, including cell growth and tissue injury repair following myocardial ischaemia reperfusion [11], neurological stroke [12] and inflammation [13]. In recent years, research on the mechanism of miRNA transfer, including exosomes, has attracted increasing attention [14,15].…”