A study led by a Clínic-IDIBAPS team has discovered that the miR122, the most abundant microRNA in the liver, plays a dual and context-dependent role in the process of liver regeneration. The results, published in the International Journal of Molecular Sciences, show that while inhibition of miR122 accelerates regeneration in a healthy liver, its absence in a liver with fibrosis causes pathological regeneration leading to liver failure.
Liver regeneration is an essential mechanism following liver resection. However, in patients with chronic liver disease, this process frequently fails, considerably increasing the risk of mortality. Although miR122 has been extensively studied within the context of liver cancer, its role in liver regeneration had not previously been explored in depth.
To address this question, the research team generated a mouse model that does not express miR122 and analysed liver regeneration following partial hepatectomy, both in healthy livers and livers with induced fibrosis. In healthy animals, the lack of miR122 favoured a faster entry of liver cells into the cell cycle, accelerating tissue regeneration. On the other hand, within the fibrotic context, this same absence triggered a worsening of the fibrosis, severe metabolic dysregulation, oxidative stress, and inflammation.
"This study shows that increasing cell proliferation is not enough if the tissue cannot maintain its metabolic function," explains Manel Morales, head of the IDIBAPS Biomarkers and laboratory precision medicine in hepatology, metabolism, and rare diseases (HEMERA-Lab) group, CIBERehd researcher and leader of the work.
According to Jordi Ribera, first author of the study, group researcher and also a member of CIBERehd, and Anna Cardona, a predoctoral researcher in the group, "our results help to explain why patients with fibrosis or cirrhosis have such a high risk of liver failure. The decrease in miR122 is not only an indicator of disease, but a factor that directly contributes to regenerative failure”.
The conclusions of the study suggest that miR122 is essential for ensuring functional liver regeneration in damaged livers, opening the door to future therapeutic strategies aimed at restoring or modulating this microRNA in patients with chronic liver disease. This knowledge could help, in the long term, to improve the safety of liver surgeries as well as the prognosis for these patients.
