Serum thrombospondin 2 is a novel predictor for the severity in the patients with NAFLD

Abstract

Aim Thrombospondins are a family of multidomain and secretory glycoproteins. Among them, thrombospondin 2 (TSP2) encoded by TSP2 gene has been reported to be involved in various functions such as collagen/fibrin formation, maintenance of normal blood vessel density and cell adhesion properties. Microarray analyses ranked TSP2 as one of the most highly up‐regulated genes in the fibrotic liver in patients with non‐alcoholic fatty liver disease (NAFLD). Since TSP2 possesses unique properties as a secretory protein, we hypothesized that hepatic TSP2 gene expression levels would be reflected in serum TSP2 levels. In this study, we examined the relationship between serum TSP2 concentrations and clinicopathological findings in NAFLD patients. Methods One hundred and thirty NAFLD patients who had undergone liver biopsy between 2009 and 2015 were retrospectively enrolled. Serum samples were collected at the time of biopsy, and TSP2 was measured by enzyme immunoassays. Results Serum TSP2 levels moderately correlated with ballooning (r = 0.56, P < .001) and fibrosis stage (r = 0.53, P < .001). The AUC values of TSP2 for predicting mild fibrosis (≧F1), moderate fibrosis (≧F2) and severe fibrosis (≧F3) were 0.73, 0.76 and 0.82 respectively. Additionally, NAFLD activity score (NAS) correlated best with TSP2 (r = 0.52, P < .001) compared to conventional NAFLD‐related biomarkers, such as cytokeratin 18 M30, hyaluronic acid, type IV collagen 7S, APRI and FIB‐4 index. Conclusion Serum TSP2 levels reflected hepatocyte ballooning, fibrosis and NAS in NAFLD patients. For clinical application of serum TSP2 as a predictor of NAFLD histological activity, additional validation and mechanistic investigations are required.

Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD

“…Proteomics studies have also shown increased fibulin-5 protein levels with hepatic fibrosis 27 and recent functional studies show that fibulin-4 is essential for elastin and collagen fiber crosslinking and extracellular matrix assembly via lysyloxidase (LOX) 28 . THBS2 (thrombospondin-2) also encodes a secreted ECM glycoprotein, which modestly correlates with histologic severity of NASH and fibrosis in a recent study 29 .…”

Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment

“…TSP2 is involved in multiple processes such as collagen/fibrin formation. TSP2 had an AUROC of 0.82 for prediction of ≥F3 (192). Lastly, the serum marker type IV collage 7s can be used to diagnose significant fibrosis with an AUROC of 0.832, a sensitivity of 91.4%, and a NPV of 87.9% with a cut-off value of ≥5.2 ng/mL (193).…”

Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway

“…TSP2 was proposed as prognosis marker in liver fibrosis, 47,48 non-alcoholic fatty liver disease, 49 and different cancers. [50][51][52][53] This study demonstrates that TSP2 is an important player in OA pathogenesis, with a positive correlation observed between TSP2 expression and synovial tissue inflammation, suggesting TSP2 could been developed as novel osteoarthritis marker.…”