Pressure suppresses hepatocellular glycogen synthesis through activating the p53/Pten pathway

Abstract

Portal hypertension is the primary cause of complications in patients with chronic liver diseases, and markedly impacts metabolism within the nervous system. Until recently, the role of portal hypertension in hepatocellular metabolism was unclear. The present study demonstrated that an increase in extracellular pressure significantly decreased hepatocellular glycogen concentrations in HepG2 and HL-7702 cells. In addition, it reduced glycogen synthase activity, by inhibiting the phosphorylation of glycogen synthase 1. RNA-seq analysis revealed that mechanical pressure suppressed glycogen synthesis by activating the p53/phosphatase and tensin homolog pathway, further suppressing glycogen synthase activity. The present study revealed an association between mechanical pressure and hepatocellular glycogen metabolism, and identified the regulatory mechanism of glycogen synthesis under pressure.

Overexpression of pressure-responsive miRNA-5703 inhibits pressure-induced growth and metastasis of liver cancer

“…The 2-dimensional (2D) pressure loading system was designed and manufactured by our research group, and the protocol can be found in our previous papers [14,29,30]. The Flexcell-5000 Compression System (Flexcell International Corp, Burlington, NC, US) was used to exert pressure on the 3D cultured cells.…”