Choline Kinase Alpha Is a Novel Transcriptional Target of the Brg1 in Hepatocyte: Implication in Liver Regeneration
- Front Cell Dev Biol. 2021 Aug 6:9:705302. doi: 10.3389/fcell.2021.705302.
- 1. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Department of Pathophysiology, Collaborative Innovation Center for Cardiovascular Translational Medicine, Nanjing Medical University, Nanjing, China.
- 2. Institute of Biomedical Research, Liaocheng University, Liaocheng, China.
- 3. Department of Pathology, Nanjing Drum Tower Hospital Affiliated with Nanjing University School of Medicine, Nanjing, China.
- 4. College of Life Sciences, Liaocheng University, Liaocheng, China.
- 5. Division of Life Sciences and Medicine, Department of Pathology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, China.
- 6. Division of Life Sciences and Medicine, Intelligent Pathology Institute, University of Science and Technology of China, Hefei, China.
- 7. Department of Cell Biology, The Municipal Laboratory of Liver Protection and Regulation of Regeneration, School of Basic Medical Sciences, Beijing, China.
Liver regeneration is a key compensatory process in response to liver injury serving to contain damages and to rescue liver functions. Hepatocytes, having temporarily exited the cell cycle after embryogenesis, resume proliferation to regenerate the injured liver parenchyma. In the present study we investigated the transcriptional regulation of Choline Kinase alpha (Chka) in hepatocytes in the context of liver regeneration. We report that Chka expression was significantly up-regulated in the regenerating livers in the partial hepatectomy (PHx) model and the acetaminophen (APAP) injection model. In addition, treatment with hepatocyte growth factor (HGF), a strong pro-proliferative cue, stimulated Chka expression in primary hepatocytes. Chka depletion attenuated HGF-induced proliferation of hepatocytes as evidenced by quantitative PCR and Western blotting measurements of pro-proliferative genes as well as EdU incorporation into replicating DNA. Of interest, deletion of Brahma-related gene 1 (Brg1), a chromatin remodeling protein, attenuated Chka induction in the regenerating livers in mice and in cultured hepatocytes. Further analysis revealed that Brg1 interacted with hypoxia-inducible factor 1 alpha (HIF-1α) to directly bind to the Chka promoter and activate Chka transcription. Finally, examination of human acute liver failure (ALF) specimens identified a positive correlation between Chka expression and Brg1 expression. In conclusion, our data suggest that Brg1-dependent trans-activation of Chka expression may contribute to liver regeneration.