Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Increases in Patients With Obstructive Jaundice through the Activation of Hepatic Stellate Cells by Bile Acids.

Abstract

Background: Mac-2 binding protein glycosylation isomer (M2BPGi) is a reliable serum marker for assessing liver fibrosis and is secreted by hepatic stellate cells (HSCs). However, M2BPGi is a known marker of dynamic fluctuations that reflects liver fibrosis, and factors including liver injury and hepatocyte regeneration. Obstructive jaundice (OJ) causes bile acid accumulation and subsequent liver injury. We aimed to evaluate the changes in M2BPGi levels in patients with OJ and elucidate whether HSC activation by bile acids increases M2BPGi levels.

Methods: In total, 220 patients who underwent pancreatobiliary surgery were analyzed; the M2BPGi levels before and after biliary drainage were evaluated in 60 patients with OJ. Activation of HSCs (LX-2 cells) treated with bile acids (cholic acid, deoxycholic acid, and lithocholic acid) and the subsequent secretion of M2BPGi were evaluated by western blotting and coimmunoprecipitation.

Results: M2BPGi levels were significantly higher in patients with OJ, strongly correlating with total bilirubin levels in laboratory data. Among the 60 patients with OJ, 51 showed decreased M2PBGi levels after biliary drainage; nine showed increased levels, even after biliary drainage. Cholangitis during biliary drainage was more common in patients with increased M2BPGi levels. Cholic acid-treated LX-2 cells upregulated α-SMA expression and M2BPGi secretion in culture media relative to non-treated LX-2 cell.

Conclusions: M2BPGi levels are significantly higher in patients with than without OJ due to the activation of HSCs by bile acids. M2BPGi levels are improved by biliary drainage, and the presence of prolonged liver dysfunction, and inflammation (such as cholangitis) appears to induce prolonged M2BPGi elevation.

Trial registration: HS2023-100.