| Category |
Gastroenterology & Hepatology |
| Manuscript Type |
Basic Study |
| Article Title |
Dysregulated signal transducer and activator of transcription 3 drives intestinal permeability and may contribute to acute-on-chronic liver failure
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
Nikolai Leinz, Sandra Beyer, Babithra Yoganathan-Kugarajan, Nico Kraus, Cristina Ortiz, Lisa Hahnefeld, Robert Gurke, Marion Başoğlu, Guido Plotz, Stefan Eimer, Stefan Zeuzem, Jonel Trebicka, Christoph Welsch and Angela Brieger |
| Funding Agency and Grant Number |
| Funding Agency |
Grant Number |
| LOEWE Research Program (Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz) of the State of Hessen (HMWK) within the ACLF- Research Initiative |
No. ACLF-I |
| University Hospital Frankfurt “Programm Nachwuchswissenschaftler” |
|
| Verein Leberforschung Frankfurt e.V |
|
| German Research Foundation (DFG) |
No. 445757098 |
| German Research Foundation (DFG) |
No. SFB 1039 Z01 |
|
| Corresponding Author |
Angela Brieger, PhD, Professor, Senior Scientist, Goethe University Frankfurt, University Hospital, Medical Clinic 1, Biomedical Research Laboratory, Theodor-Stern-Kai 7, Frankfurt 60590, Hesse, Germany. a.brieger@em.uni-frankfurt.de |
| Key Words |
Acute-on-chronic liver failure; Cirrhosis; Gut barrier dysfunction; Signal transducer and activator of transcription 3; Tight junctions |
| Core Tip |
Intestinal barrier disfunction is frequently observed in acute-on-chronic liver failure (ACLF) secondary to chronic liver disease, yet the underlying molecular mechanisms remain largely unknown. This study identifies a disrupted expression pattern of the intestinal signal transducer and activator of transcription 3 (STAT3) as a central regulator of epithelial barrier integrity during the course of liver disease. Dysregulated STAT3 significantly impairs tight junction architecture and epithelial morphology, leading to increased intestinal permeability. The accumulation of unphosphorylated STAT3, independent of canonical STAT3 phosphorylation, may represent a potential biomarker linking cirrhosis to ACLF and could serve as a novel therapeutic target. |
| Citation |
Leinz N, Beyer S, Yoganathan-Kugarajan B, Kraus N, Ortiz C, Hahnefeld L, Gurke R, Başoğlu M, Plotz G, Eimer S, Zeuzem S, Trebicka J, Welsch C, Brieger A. Dysregulated signal transducer and activator of transcription 3 drives intestinal permeability and may contribute to acute-on-chronic liver failure. World J Gastroenterol 2026; In press |
