Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH).
Savneet Kaur, Preety Rawal, Hamda Siddiqui, Sumati Rohilla, Shvetank Sharma, Dinesh M Tripathi, Sukriti Baweja, Mohsin Hassan, Sebastian Vlaic, Reinhard Guthke, Maria Thomas, Rania Dayoub, Chaggan Bihari, Shiv K Sarin, Thomas S Weiss
Author Information
Savneet Kaur: Institute of Liver and Biliary Sciences, New Delhi-110070, India. savykaur@gmail.com.
Preety Rawal: Gautam Buddha University, Greater Noida-201308, India. rawal.prets86@gmail.com.
Hamda Siddiqui: Institute of Liver and Biliary Sciences, New Delhi-110070, India. hamda101@yahoo.com.
Sumati Rohilla: Gautam Buddha University, Greater Noida-201308, India. sumatir101@gmail.com.
Shvetank Sharma: Institute of Liver and Biliary Sciences, New Delhi-110070, India. shvetanks@gmail.com.
Dinesh M Tripathi: Institute of Liver and Biliary Sciences, New Delhi-110070, India. dineshmanitripathi@gmail.com.
Sukriti Baweja: Institute of Liver and Biliary Sciences, New Delhi-110070, India. sukritibiochem@gmail.com.
Mohsin Hassan: Institute of Liver and Biliary Sciences, New Delhi-110070, India. ol.mohsin@gmail.com.
Sebastian Vlaic: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll-Institute, 07745 Jena, Germany. bastivl@gmail.com.
Reinhard Guthke: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll-Institute, 07745 Jena, Germany. gr.guthke@gmx.de.
Maria Thomas: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, and University of Tuebingen, 72076 Tuebingen, Germany. thomasmasha@gmail.com.
Rania Dayoub: University Children Hospital (KUNO), University Hospital of Regensburg, 93053 Regensburg, Germany. Rania.Dayoub@ukr.de.
Chaggan Bihari: Institute of Liver and Biliary Sciences, New Delhi-110070, India. drcbsharma@gmail.com.
Shiv K Sarin: Institute of Liver and Biliary Sciences, New Delhi-110070, India. Rania.Dayoub@ukr.de.
Thomas S Weiss: University Children Hospital (KUNO), University Hospital of Regensburg, 93053 Regensburg, Germany. thomas.weiss@ukr.de.
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 in NASH. The gene expression of 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 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- significantly induced the expression of in ECs. regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of . Furthermore, increased the angiogenic activity of ECs. This study reports that steatosis-induced augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH.
