The adaptor protein alpha-syntrophin is reduced in human non-alcoholic steatohepatitis but is unchanged in hepatocellular carcinoma

Exp Mol Pathol. 2017 Oct;103(2):204-209. doi: 10.1016/j.yexmp.2017.09.005. Epub 2017 Sep 21.

Abstract

The adaptor protein alpha-syntrophin (SNTA) is differentially expressed in varying types of cancer and affects triglyceride levels, inflammatory response and cell proliferation. However, little is known about the expression of SNTA in liver diseases. Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation and eventually fibrosis, and may progress to hepatocellular carcinoma (HCC). Here, SNTA mRNA was analyzed in liver tissues from 71 non-alcoholic fatty liver disease patients and 32 controls to assess associations with disease characteristics. SNTA mRNA expression was reduced in NASH liver and negatively correlated with steatosis, inflammation, fibrosis and NASH scores. In the NASH patients, those with type 2 diabetes had a higher fibrosis score, reduced inflammation and increased hepatic SNTA mRNA levels demonstrating a strong association of SNTA mRNA levels with inflammation. Recently, we have shown diminished expression of the high-density lipoprotein scavenger receptor BI (SR-BI) in the liver of syntrophin-deficient mice. Indeed, hepatic SNTA and SR-BI mRNA were positively correlated. SNTA protein was further determined in tumor and non-tumorous tissues of 21 HCC patients. Protein expression was unchanged in the tumor and not related to staging and grading. Present study identified associations of hepatic SNTA mRNA levels with SR-BI and features of NASH assuming a function of this protein in chronic liver disease and cholesterol metabolism.

Keywords: Inflammation; Malignancy; SR-BI; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Diagnosis, Differential
  • Female
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Scavenger Receptors, Class B / genetics
  • Scavenger Receptors, Class B / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • syntrophin alpha1