Handling Editor: Elaine R. Mardis
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: R.R., D.C., A.E.; Methodology: R.R., D.C., M.M., L.M., F.G.; Validation: D.C., D.S.; Formal analysis: D.C., L.M., F.G., C.B., I.C., A.E.; Investigation: R.R., M.M., D.S., L.M., F.G., M.C.B., C.B., I.C., A.E.; Data curation: R.R., D.C., D.S., M.C.B., A.E.; Writing - original draft: R.R., D.C., C.B., I.C., A.E.; Writing - review & editing: R.R., D.C., M.C.B., C.B., I.C., A.E.; Supervision: A.E.; Project administration: A.E.; Funding acquisition: A.E.
Funding
This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC 2014 Grant IG15461 to A.E.), Associazione Italiana Glicogenosi (to A.E.), Compagnia di San Paolo (Grant 318 to A.E.) and Ministero della Salute (Ricerca Corrente).
Data availability
The raw file from each array card experiment has been deposited at the Gene Expression Omnibus (GEO) public repository at NCBI (http://www.ncbi.nlm.nih.gov) and can be accessed through GEO series accession number GSE157656.
Supplementary information
Supplementary information available online at https://dmm.biologists.org/lookup/doi/10.1242/dmm.043364.supplemental
- Received November 7, 2019.
- Accepted June 23, 2020.
- © 2020. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.