Key Laboratory of Regenerative Medicine of Ministry of Education, Department of Developmental & Regenerative Biology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
Published: June 2022
AI Article Synopsis
Article Abstract
Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3 mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.
Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Liver tissue engineering holds promising in synthesizing or regenerating livers, while the design of functional scaffold remains a challenge. Owing to the intricate simulation of extracellular matrix structure and performance, porous scaffolds have demonstrated advantages in creating liver microstructures and sustaining liver functions. Currently, various methods and processes have been employed to fabricate porous scaffolds, manipulating the properties and morphologies of materials to confer them with unique supportive functions.
Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2.
Institute of Tissue Regeneration, Soonchunhyang University, Cheonan 31151, Republic of Korea; Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea.
Although hemostatic powders are commonly used in clinical and emergency settings, they frequently show poor absorption, raise cytotoxicity issues, and are not effective for fatal non-compressible bleeding. The purpose of this research is to create a self-gelling hemostatic powder based on chitosan, bentonite, and sodium polyacrylate (CBS) to improve the hemostatic effect. When liquid comes into contact with CBS powders, they can fuse and form a stable hydrogel in less than 30s.
To investigate the promoting effect of extracellular vesicles derived from myocardial cells (CM-EVs) on the reprogramming of cardiac fibroblasts (CFs) into cardiomyocyte-like cells (iCMs) and their therapeutic effect on myocardial infarction (MI) in rats. Cell experiments: The differential adhesion method was used to obtain Sprague Dawley (SD) suckling rat CFs and cardiomyocytes (CMs), while the ultracentrifugation method was used to obtain CM-EVs. Transmission electron microscopy and nanoparticle tracking technology were used to analyze and determine the morphology and particle size of CM-EVs.
