To investigate the different expression profiles of MAPK pathway genes and their corresponding functions during liver regeneration, we used a CCl4 induced mouse liver regeneration model in this study. Mouse was injected with CCl4 in the abdominal cavity to cause damage in the liver and followed by liver histology examination and measurement of serum ALT levels in blood sample collected at 0, 0.5, 1.5, 4.5, and 7 d after CCl4 injection. Differentially expressed genes in the MAPK pathway during liver regeneration were analyzed using mouse cDNA microarray method (Affymetrix). The results obtained were further subjected to hierarchical clustering study and were validated with real-time PCR. Microarray hybridization identified 31 out of the 93 MAPK pathway component genes, which have significantly altered their expression levels during liver regeneration. Among them, both up- and down-regulated genes were classified into various groups according to clustering studies and functional analysis. At the initial stage of liver regeneration, the number of up-regulated genes was greater than the down-regulated genes, while at the late stage the situation was reversed. Our results suggest that MAPK pathway might play different regulatory roles in responding to different stages of liver regeneration.
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http://dx.doi.org/10.3724/sp.j.1005.2010.01043 | DOI Listing |
Nat Biotechnol
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.
View Article and Find Full Text PDFCell Signal
January 2025
Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan 030001, China. Electronic address:
Hepatic stellate cells (HSCs) are the central link of the occurrence and development of hepatic fibrosis, and autophagy promotes HSCs activation. N6-methyladenosine (m6A) RNA modification can also control autophagy by targeting selected autophagy-associated genes. but up to now, little research has been done on the m6A modification autophagy-related genes (ATGs) in hepatic fibrosis.
View Article and Find Full Text PDFLife Med
February 2024
Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.
In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians.
View Article and Find Full Text PDFHPB (Oxford)
December 2024
Institute for Clinical Research (IKF), Semmelweis University, Campus Hamburg, Germany; Division of HPB Surgery, Department of Surgery, Asklepios Hospital Barmbek, Hamburg, Germany. Electronic address:
Background: The two-stage surgical technique of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) enables extensive liver resection and promotes future liver remnant regeneration (FLR), in part by inhibiting the Hippo signalling pathway. Its main effector, Yes-associated protein (YAP), has low intrinsic transcriptional activity and requires the transcription enhanced associated domain factor (TEAD) family members as cofactors for target gene transcription. We evaluated the intracellular localization and expression of TEAD1-4, hypothesized to regulate the activity of YAP and, consequently, liver regeneration.
View Article and Find Full Text PDFBackground And Aims: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is reversible at early stages, making early identification of high-risk individuals clinically valuable. Previously, we demonstrated that patient-derived induced pluripotent stem cells (iPSCs) harboring MASLD DNA risk variants exhibit greater oleate-induced intracellular lipid accumulation than those without these variants. This study aimed to develop an iPSC-based MASLD risk predictor using functional lipid accumulation assessments.
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