Serum miR‑29 is increased in mice with early liver fibrosis

• Published in: Experimental and therapeutic medicine 2024-07, Vol.28 (1), Article 285
• Main Authors: Matsumoto, Kana, Ohsugi, Yuhei, Tayama, Chisa, Hayashi, Momone, Kato, Yumiko, Ohashi, Mizuho, Chiba, Mitsuru
• Format: Article
• Language: English
• Subjects: Anesthesia; Biological markers; Biomarkers; Biopsy; Development and progression; Diet; Ethanol; Fibrosis; Health aspects; Identification and classification; Liver cirrhosis; Liver diseases; Measurement; MicroRNA; MicroRNAs; Respiration; Risk factors
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2024.12573

Non-alcoholic steatohepatitis (NASH) is a fatty liver disease that is not caused by alcohol consumption and is characterized by fatty degeneration, inflammation and hepatocellular damage. Therefore, predicting future fibrosis is critical in the early stages of NASH to prevent disease progression. The present study examined histological changes in the liver as well as microRNA (miR/miRNA) expression changes in the liver and serum of NASH mice model to identify potential biomarker candidates that could predict early fibrosis. This study used 6-week-old C57BL/6NJcl male mice and fed the control with a standard solid diet (CE-2) for breeding and propagation and NASH groups with a high-fat diet [choline-deficient high-fat and 0.1% (w/v) methionine supplemented diet], respectively. Agilent Technologies miRNA microarray was used to investigate microRNA expression in the liver and serum. Hematoxylin and eosin staining of the livers of the NASH group mice during the second week of feeding revealed fatty degeneration, balloon-like degeneration and inflammatory cell infiltration, confirming that the mice were in a state of NASH. The livers of the NASH group mice at 6 weeks of feeding showed fibrosis. Microarray analysis revealed that miRNAs were upregulated and 47 miRNAs were downregulated in the liver of the NASH group. Pathway analysis using OmicsNet predicted miR-29 to target collagen genes. Furthermore, miR-29 was downregulated in the livers of NASH-induced mice but upregulated in serum. These findings suggested that lower miR-29 expression in NASH-induced liver would increase collagen expression and fibrosis. Early liver fibrosis suggests that miR-29 leaks from the liver into the bloodstream, and elevated serum miR-29 levels may be a predictive biomarker for early liver fibrosis.