Liver-specific depletion of an endosomal regulator causes apoptosis, cell death and liver failure

The endosomal regulators play a key role in signal transduction and the recycling of plasma membrane proteins. However, little is known about the function of these regulators in physiology in the liver. To identify the role of one of the regulators in liver we did the adenovirus mediated liver-specific KD in adult mice. Loss of this regulator induces severe liver inflammation and organ damage leading to animal lethality after 10 days of RNAi. This is associated with significantly decreased blood glucose and elevated aspartate aminotransferase and alanine aminotransferase levels in the serum. Reduction of this regulator in the liver causes a time dependent activation of liver inflammation, apoptosis and cell death, accumulating into a lethal phenotype in mice. Moreover, we find its expression is decreased in patients with NASH and to negatively correlate with the inflammation markers IL6 and IL1b in humans, highlighting its potential regulatory function in liver diseases.

Publication History

Article published online:
26 January 2022