Kaur, Savneet and Rawal, Preety and Siddiqui, Hamda and Rohilla, Sumati and Sharma, Shvetank and Tripathi, Dinesh M. and Baweja, Sukriti and Hassan, Mohsin and Vlaic, Sebastian and Guthke, Reinhard and Thomas, Maria and Dayoub, Rania and Bihari, Chaggan and Sarin, Shiv K. and Weiss, Thomas S. (2019) Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH). CELLS, 8 (10): 1277. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
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-beta 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEMATOPOIETIC STEM-CELLS; KINASE C-EPSILON; GROWTH-FACTOR; INSULIN-RESISTANCE; ANGIOGENESIS; TRANSCRIPTION; MACROPHAGES; MECHANISM; FIBROSIS; GENES; angiogenesis; inflammation; non-alcoholic fatty liver disease; fatty liver; steatosis; RUNX1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 05:46 |
| Last Modified: | 31 Mar 2020 06:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26061 |
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