Promotion of NR1I3-mediated liver growth is accompanied by STAT3 activation

• Published in: Molecular biology reports Vol. 49; no. 5; pp. 4089 - 4093
• Main Authors: Mazin, Mark E., Yarushkin, Andrei A., Pustylnyak, Yuliya A., Prokopyeva, Elena A., Pustylnyak, Vladimir O.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2022; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Benzene; Binding sites; Biomedical and Life Sciences; Cell cycle; Cell growth; Cell Proliferation; Cyclin D1; Gene expression; Hepatocytes - physiology; Histology; Hydrocarbons; Immunofluorescence; Laboratory animals; Life Sciences; Liver; Mice; Mice, Inbred C57BL; Molecular biology; Morphology; Phosphorylation; Proteins; Receptors, Cytoplasmic and Nuclear - genetics; Short Communication; Signal Transduction; Stat3 protein; Hepatocyte proliferation; CAR; Liver; Liver hyperplasia; STAT3
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07340-1

Background The constitutive androstane receptor (CAR, NR1I3)-mediated mechanisms regulating hepatocyte proliferation and growth of the liver did not yet experience complete elucidation. We investigated whether STAT3 could be activated in vivo by NR1I3 signaling in mouse liver. Methods and results Using Western blot analysis, immunofluorescence assays and real-time PCR we established the state of STAT3 activation when it comes to the mouse liver subsequent to treatment ofNR1I3 agonist,1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). STAT3 nuclear relocation and hepatocyte growth were both induced by NR1I3-mediated phosphorylation of STAT3. Moreover, the NR1I3-STAT3 signaling pathway’s proliferation impact was facilitated, partly, by cMyc and Cyclin D1 upregulation. Conclusions This work’s evidence demonstrates that NR1I3-pushed STAT3 activation contributes to TCPOBOP-induced liver growth and hepatocyte proliferation, at least in part, through its molecular targets cMyc and CyclinD1.