Several previous reports indicated that partial hepatectomy (PH) when combined with splenectomy enhances the regenerative capacity of the liver, most probably due to the removal of unknown inhibitory factors released from the spleen. Transforming growth factor (TGF)-beta1 is a major antiproliferative factor for the hepatocytes, and the role of splenic TGF-beta1 in liver regeneration is yet to be clarified. The splenic expression of TGF-beta1 and its secretion into the portal circulation from the spleen were evaluated in a standardized two-thirds hepatectomy model in rats. Rats in the control group underwent only the hepatectomy, while splenectomy was added in the splenectomy group. The hepatocyte proliferation rate was assessed by proliferating cell nuclear antigen (PCNA) immunostaining, and the results were compared with the TGF-beta1 kinetics in the portal blood. Significant increase in PCNA index and decrease in portal TGF-beta1 level were noticed in the splenectomy group at 48 hours after PH compared with the control group. Both TGF-beta1 protein and mRNA expression level in the spleen were strongest at 48 hours after PH and coincided with the peak of the plasma TGF-beta1 level. TGF-beta type II receptor (TbetaR-II) expression in the liver after PH was assessed immunohistochemically. The expression of TbetaR-II decreased at 12 hours and returned to preoperative level at 24 hours after PH in both groups. The changes of TbetaR-II expression were similar in both groups, and the significant difference was not observed at 48 hours after PH. Namely, splenectomy did not alter the expression of TbetaR-II in remnant liver at the peak of hepatocytes proliferation. In conclusion we found that TGF-beta1 was produced and secreted by the spleen during the early phase of liver regeneration and removal of the spleen enhanced proliferation of hepatocytes. Splenectomy thus may exert a salutary effect in selected patients with jeopardized regenerative capacity of the liver.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/01.lab.0000095686.10639.c8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.
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 PDFm6A modified ATG9A is required in regulating autophagy to promote HSCs activation and liver fibrosis.
Cell 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 PDFA biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.
Life 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 PDFTranscription enhanced associate domain factor 1 (TEAD1) predicts liver regeneration outcome of ALPPS-treated patients.
HPB (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.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!