ArticleJournal of cell science2013
Lamin aggregation is an early sensor of porphyria-induced liver injury.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Porphyrias: Pathophysiology and clinical management recommendations for hepatologists.Hepatology communications · 2025Review
- Animal Models of Porphyria with Hepatic Involvement.Seminars in liver disease · 2025Review
- Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches.World journal of hepatology · 2025Review
- BALB.NCT-Molecular genetics and metabolism reports · 2023Article
- Review
- Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications.Diagnostics (Basel, Switzerland) · 2021Review
- Drosophila p38 MAPK interacts with BAG-3/starvin to regulate age-dependent protein homeostasis.Aging cell · 2021Article
- Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for Porphyria-Mediated Hepatocytotoxicity.Toxicologic pathology · 2021Article
- Acitretin mitigates uroporphyrin-induced bone defects in congenital erythropoietic porphyria models.Scientific reports · 2021Article
- Geographic prevalence variation and phenotype penetrance in porphyria: insights from a Chinese population database.Blood advances · 2021Article
- A Novel Mechanism for NF-κB-activation via IκB-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation.Molecular & cellular proteomics : MCP · 2020Article
- Porphyrin-Induced Protein Oxidation and Aggregation as a Mechanism of Porphyria-Associated Cell Injury.Cellular and molecular gastroenterology and hepatology · 2019Review
- Loss of hepatocyte β-catenin protects mice from experimental porphyria-associated liver injury.Journal of hepatology · 2019Article
- Oxygen and Conformation Dependent Protein Oxidation and Aggregation by Porphyrins in Hepatocytes and Light-Exposed Cells.Cellular and molecular gastroenterology and hepatology · 2019Article
- Lamins and Lamin-Associated Proteins in Gastrointestinal Health and Disease.Gastroenterology · 2018Review
- Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.Hepatology (Baltimore, Md.) · 2018Article
- Hepatocyte-Specific Deletion of Mouse Lamin A/C Leads to Male-Selective Steatohepatitis.Cellular and molecular gastroenterology and hepatology · 2017Article
- Upregulated heme biosynthesis, an exploitable vulnerability in MYCN-driven leukemogenesis.JCI insight · 2017Article
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Oxidative liver injury during steatohepatitis results in aggregation and transglutaminase-2 (TG2)-mediated crosslinking of the keratin cytoplasmic intermediate filament proteins (IFs) to form Mallory-Denk body (MDB) inclusions. The effect of liver injury on lamin nuclear IFs is unknown, though lamin mutations in several human diseases result in lamin disorganization and nuclear shape changes. We tested the hypothesis that lamins undergo aggregation during oxidative liver injury using two MDB mouse models: (i) mice fed the porphyrinogenic drug 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and (ii) mice that harbor a mutation in ferrochelatase (fch), which converts protoporphyrin IX to heme. Dramatic aggregation of lamin A/C and B1 was noted in the livers of both models in association with changes in lamin organization and nuclear shape, as determined by immunostaining and electron microscopy. The lamin aggregates sequester other nuclear proteins including transcription factors and ribosomal and nuclear pore components into high molecular weight complexes, as determined by mass-spectrometry and confirmed biochemically. Lamin aggregate formation is rapid and precedes keratin aggregation in fch livers, and is seen in liver explants of patients with alcoholic cirrhosis. Exposure of cultured cells to DDC, protoporphyrin IX or N-methyl-protoporphyrin, or incubation of purified lamins with protoporphyrin IX, also results in lamin aggregation. In contrast, lamin aggregation is ameliorated by TG2 inhibition. Therefore, lamin aggregation is an early sensor of porphyria-associated liver injury and might serve to buffer oxidative stress. The nuclear shape and lamin defects associated with porphyria phenocopy the changes seen in laminopathies and could result in transcriptional alterations due to sequestration of nuclear proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.