Vasorin Deletion in C57BL/6J Mice Induces Hepatocyte Autophagy through Glycogen-Mediated mTOR Regulation.

Abnormal vasorin () expression occurs in multiple diseases, particularly liver cancers. knockout (KO) in mice causes malnutrition, a shortened life span, and decreased physiological functions. However, the causes and underlying mechanisms remain unknown. Here, we established KO C57BL/6J mice by using the CRISPR/Cas9 system. The animals were weighed, and histology, immunohistochemistry, electronic microscopy, and liver function tests were used to examine any change in the livers. Autophagy markers were detected by Western blotting. MicroRNA (miRNA) sequencing was performed on liver samples and analyses to study the signaling pathway altered by KO. Significant reductions in mice body and liver weight, accompanied by abnormal liver function, liver injury, and reduced glycogen accumulation in hepatocytes, were observed in the KO mice. The deficiency of also significantly increased the number of autophagosomes and the expression of LC3A/B-II/I but decreased SQSTM1/p62 levels in hepatocytes, suggesting aberrant activation of autophagy. deficiency inhibited glycogen-mediated mammalian target of rapamycin (mTOR) phosphorylation and activated Unc-51-like kinase 1 (ULK1) signaling, suggesting that deletion upregulates hepatocyte autophagy through the mTOR-ULK1 signaling pathway as a possible cause of diminished life span and health. Our results indicate that is required for the homeostasis of liver glycogen metabolism upstream of hepatocyte autophagy, suggesting research values for regulating in pathways related to liver physiology and functions. Overall, this study provides new insight into the role of in liver functionality.