Periostin Circulating Levels and Genetic Variants in Patients with Non-Alcoholic Fatty Liver Disease.

Carlo Smirne,Nadia Barizzone,Matteo Nazzareno Barbaglia,Rosalba Minisini,Elena Grossini,Venkata Ramana Mallela,Michela Emma Burlone,Violante Mulas,Mario Pirisi

doi:10.3390/diagnostics10121003

Carlo Smirne, Nadia Barizzone + Show 7 more

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https://doi.org/10.3390/diagnostics10121003

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Abstract

Circulating periostin has been suggested as a possible biomarker in non-alcoholic fatty liver disease (NAFLD) in Asian studies. In the present study, we aimed to test its still controversial relevance in a Caucasian population. In patients with histologically-proven NAFLD (N. = 74; 10 with hepatocellular carcinoma, HCC) plasma periostin concentrations were analyzed. POSTN haplotype analysis was based on rs9603226, rs3829365, and rs1029728. Hepatitis C patients (N. = 81, 7 HCC) and healthy subjects (N. = 27) were used as controls. The median plasma periostin concentration was 11.6 ng/mL without differences amongst groups; it was not influenced by age, liver fibrosis or steatosis. However, possession of haplotype two (rs9603226 = G, rs3829365 = C, rs1028728 = A) was associated with lower circulating periostin compared to other haplotypes. Moreover, periostin was higher in HCC patients. At multivariate analysis, HCC remained the only predictor of high periostin. In conclusion, plasma periostin concentrations in Caucasians NAFLD patients are not influenced by the degree of liver disease, but are significantly higher in HCC. Genetically-determined differences may account for some of the variability. These data suggest extreme caution in predicting a possible future role of periostin antagonists as a rational therapeutic alternative for NAFLD, but show a potential periostin role in the management of NAFLD-associated HCC.

Highlights

Non-alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease worldwide, includes a spectrum of chronic diseases ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH)
Hepatic inflammation and fibrosis were significantly inhibited in PN-knockout mice, mainly through a transforming growth factor (TGF)-β1 and TGF-β2 dependent mechanism, revealing a potential role of PN in NASH [9,15]
It should be emphasized that PN belongs to the so called “liver matrisome”, which identifies the whole of extracellular matrix (ECM) and non-fibrillar proteins that interact or are structurally affiliated with the ECM, and are involved in the regulation of tissue homeostasis and organ function

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease worldwide, includes a spectrum of chronic diseases ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). PN, known as osteoblast-specific factor 2 (OSF-2), is a 90 kDa multifunctional extracellular matrix (ECM) protein, coded by periostin (POSTN) gene and mainly secreted by osteoblasts [6] It has pleiotropic activities far beyond simple bone remodeling; as a matter of fact, it is involved—amongst others—in the pathophysiology of arthritis, atherosclerosis, and inflammatory diseases [7]. One of the target organs in which PN has been shown to play a crucial role is the liver, where it can modulate the cell fate determination and proliferation, inflammatory responses, ECM remodeling, even tumorigenesis [8,9,10,11,12] In this respect, the strongest evidence so far concerns its pivotal role in the onset of metabolic disease (such as obesity and glucose or lipid disorders) by suppression of fatty acid oxidation in the liver [13]. Those events would lead to the inhibition of the PPAR-α promoter, RAR-related orphan receptor (ROR) α, and to the downregulation of PPAR-α itself [13]

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