Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH)

Cells

Preety Rawal¹  Sumati Rohilla¹  Maria Thomas²  Savneet Kaur³  Hamda Siddiqui³  Shvetank Sharma³  Mohsin Hassan³  DineshM Tripathi³  Chaggan Bihari³  Sukriti Baweja³  ShivK. Sarin³  Reinhard Guthke⁴  Sebastian Vlaic⁴  Rania Dayoub⁵  ThomasS. Weiss⁵ 

[1] Department of Biotechnology, Gautam Buddha University, Greater Noida-201308, India;Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, 72076 Tuebingen, Germany;Institute of Liver and Biliary Sciences, New Delhi-110070, India;Leibniz Institute for Natural Product Research and Infection Biology—Hans Knöll-Institute, 07745 Jena, Germany;University Children Hospital (KUNO), University Hospital of Regensburg, 93053 Regensburg, Germany;

关键词: angiogenesis;    inflammation;    non-alcoholic fatty liver disease;    fatty liver;    steatosis;    runx1;   

DOI  :  10.3390/cells8101277

来源: DOAJ

【 摘 要 】

Given the important role of angiogenesis in liver pathology, the current study investigated the role of Runt-related transcription factor 1 (RUNX1), a regulator of developmental angiogenesis, in the pathogenesis of non-alcoholic steatohepatitis (NASH). Quantitative RT-PCRs and a transcription factor analysis of angiogenesis-associated differentially expressed genes in liver tissues of healthy controls, patients with steatosis and NASH, indicated a potential role of RUNX1 in NASH. The gene expression of RUNX1 was correlated with histopathological attributes of patients. The protein expression of RUNX1 in liver was studied by immunohistochemistry. To explore the underlying mechanisms, in vitro studies using RUNX1 siRNA and overexpression plasmids were performed in endothelial cells (ECs). RUNX1 expression was significantly correlated with inflammation, fibrosis and NASH activity score in NASH patients. Its expression was conspicuous in liver non-parenchymal cells. In vitro, factors from steatotic hepatocytes and/or VEGF or TGF-β significantly induced the expression of RUNX1 in ECs. RUNX1 regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of RUNX1. Furthermore, RUNX1 increased the angiogenic activity of ECs. This study reports that steatosis-induced RUNX1 augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH.

【 授权许可】

Unknown