Thrombospondin 1 and Nuclear Factor Kappa B Signaling Pathways in Non-alcoholic Fatty Liver Disease

Abstract

Aim: We aimed to evaluate the circulating thrombospondin-1 (TSP-1) and nuclear factor kappa B (NF-κB) in nonalcoholic fatty liver disease (NAFLD) in order to integrate these signaling pathways in the inflammatory and fibrogenic processes of this liver disorder.
 Methods: Ninety-five NAFLD patients were recruited in the study. The study also included 83 age-sex matched healthy controls.
 Results: The number of patients with metabolic syndrome (MetS) criteria was 57 (60%). TSP-1 level was found to be statistically significantly lower in the NAFLD group compared to the control group (p=0.037). However, NF-κB level was found to be significantly higher in the NAFLD group compared to the control group (p=0.004). There was a significant negative correlation between plasma TSP-1 levels with glucose (r=-0.235, p=0.022), alanine aminotransferase (r=-0.261, p=0.011) and aspartate transaminase (r=-0.328, p=0.001) levels. In addition, a significant negative correlation was found between plasma TSP-1 and NF-κB levels (r=-0.729, p<0.001).
 Conclusions: Our results suggest a close relationship between increased NF-κB and reduced TSP-1 in NAFLD. TSP-1 and NF-κB signaling pathways might have a role in the inflammatory and fibrogenic processes. Furthermore, they may be used as a noninvasive marker and could assist as a therapeutic target for NAFLD.

Erythrocytes of Nonalcoholic Steatohepatitis Patients Contain Decreased Arginase-1 and Thrombospondin-1, and Increased Phosphatidylethanolamine Levels

“…Regarding the plasma TSP-1 levels, our results are in contradiction to the previous reports of other researchers. To the best of our knowledge, two studies have reported increased serum TSP-1 levels in NASH patients [25,26], and one study has reported decreased plasma TSP-1 levels [27]. In our study, we report no statistically significant difference.…”

Platelet-derived thrombospondin 1 promotes immune cell liver infiltration and exacerbates diet-induced steatohepatitis

“…Previous studies from our lab and others have established the role of TSP1 in NAFLD/NASH. 19 , 20 , 23 , 42 , 43 This study takes a step further by advancing our understanding of the specific contribution of TSP1 derived from platelets to NAFLD progression. We found that platelet-derived TSP1 does not influence the development of diet-induced steatosis.…”