ArticleThe American journal of pathology2011
Perturbations in ataxia telangiectasia mutant signaling pathways after drug-induced acute liver failure and their reversal during rescue of animals by cell therapy.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Hepatocyte Transplantation Rebalances Cytokines for Hepatic Regeneration in Rats with Ataxia Telangiectasia Mutated Pathway-Related Acute Liver Failure.The American journal of pathology · 2023Article
- HDAC6 inhibitor ACY1215 inhibits the activation of NLRP3 inflammasome in acute liver failure by regulating the ATM/F-actin signalling pathway.Journal of cellular and molecular medicine · 2021Article
- Transplantation of mesenchymal stem cells preserves podocyte homeostasis through modulation of parietal epithelial cell activation in adriamycin-induced mouse kidney injury model.Histology and histopathology · 2020Article
- Comparative analysis of the expression profiles of genes related to the Gadd45α signaling pathway in four kinds of liver diseases.Histology and histopathology · 2020Article
- Deep Learning on High-Throughput Transcriptomics to Predict Drug-Induced Liver Injury.Frontiers in bioengineering and biotechnology · 2020Article
- Efficient Reconstitution of Hepatic Microvasculature by Endothelin Receptor Antagonism in Liver Sinusoidal Endothelial Cells.Human gene therapy · 2019Article
- Artemisitene suppresses tumorigenesis by inducing DNA damage through deregulating c-Myc-topoisomerase pathway.Oncogene · 2018Article
- Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.Cell proliferation · 2018Article
- Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.Archives of toxicology · 2018Article
- Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure.Hepatology (Baltimore, Md.) · 2018Article
- Demonstrating Potential of Cell Therapy for Wilson's Disease with the Long-Evans Cinnamon Rat Model.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Ischemic preconditioning affects long-term cell fate through DNA damage-related molecular signaling and altered proliferation.The American journal of pathology · 2014Article
- Evaluation of cytotoxicity and DNA damage response with analysis of intracellular ATM signaling pathways.Assay and drug development technologies · 2014Article
- Cell therapy to remove excess copper in Wilson's disease.Annals of the New York Academy of Sciences · 2014Review
- Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms.Experimental and molecular pathology · 2013Article
- New directions for cell-based therapies in acute liver failure.Journal of hepatology · 2012Article
- Molecular perturbations restrict potential for liver repopulation of hepatocytes isolated from non-heart-beating donor rats.Hepatology (Baltimore, Md.) · 2012Article
- Spontaneous origin from human embryonic stem cells of liver cells displaying conjoint meso-endodermal phenotype with hepatic functions.Journal of cell science · 2012Article
- Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products.Differentiation; research in biological diversityArticle
- Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication.XenotransplantationArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Superior insights into molecular mechanisms of liver failure, which are not fully understood, will help strategies for inducing liver regeneration. We examined hepatotoxic mechanisms in mice homozygous for the severe combined immune deficiency mutation in the protein kinase, DNA-activated, catalytic polypeptide. Mice were treated with rifampicin, phenytoin, and monocrotaline. The ensuing acute liver failure was characterized by serological, histological, and mRNA studies. Subsequently, we studied whether transplantation of hepatocytes could rescue animals with liver failure. We found extensive liver damage in these animals, with mortality over several days. The expression of multiple hepatic genes was rapidly altered, including those representing pathways in oxidative/metabolic stress, inflammation, DNA damage-repair, and ataxia telangiectasia mutant (Atm) signaling pathways. This led to liver cell growth arrest involving cyclin-dependent kinase inhibitor 1A. Transplantation of hepatocytes with microcarriers in the peritoneal cavity efficiently rescued animals with liver failure. Molecular abnormalities rapidly reversed, including in hepatic Atm and downstream signaling pathways; and residual hepatocytes overcame cyclin-dependent kinase inhibitor 1A-induced cell growth arrest. Reseeding of the liver with transplanted hepatocytes was not required for rescue because native hepatocytes overcame cell growth-arrest to regenerate the liver. This likely resulted from paracrine signaling from hepatocytes in the peritoneal cavity. We concluded that Atm signaling played critical roles in the pathological features of liver failure. These studies should help redirect examination of pathophysiologic and therapeutic mechanisms in liver failure.
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