ArticleCell death & disease2013
Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- RAC1 as a novel therapeutic target for acute liver failure.JHEP reports : innovation in hepatology · 2025Article
- Inhibition of Rac1 attenuates radiation-induced lung injury while suppresses lung tumor in mice.Cell death discovery · 2022Article
- Osteopontin - The stirring multifunctional regulatory factor in multisystem aging.Frontiers in endocrinology · 2022Review
- miR‑375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial‑mesenchymal transition.Molecular medicine reports · 2021Article
- Role of Small GTPase RhoA in DNA Damage Response.Biomolecules · 2021Review
- Increased flux through the mevalonate pathway mediates fibrotic repair without injury.The Journal of clinical investigation · 2019Article
- Age-related response to an acute innate immune challenge in mice: proteomics reveals a telomere maintenance-related cost.Proceedings. Biological sciences · 2018Article
- Hepatocyte-specific expression of constitutively active Alk5 exacerbates thioacetamide-induced liver injury in mice.Heliyon · 2017Article
- Statins in anthracycline-induced cardiotoxicity: Rac and Rho, and the heartbreakers.Cell death & disease · 2017Review
- Rac1-Mediated DNA Damage and Inflammation Promote Nf2 Tumorigenesis but Also Limit Cell-Cycle Progression.Developmental cell · 2016Article
- Hepatitis C virus promotes hepatocellular carcinogenesis by targeting TIPE2, a new regulator of DNA damage response.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- S-Adenosylmethionine suppresses the expression of Smad3/4 in activated human hepatic stellate cells via Rac1 promoter methylation.Molecular medicine reports · 2016Article
- Rho GTPases: Novel Players in the Regulation of the DNA Damage Response?Biomolecules · 2015Review
- The role of iNOS in cholesterol-induced liver fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Rac1 GTPase-deficient HeLa cells present reduced DNA repair, proliferation, and survival under UV or gamma irradiation.Molecular and cellular biochemistry · 2015Article
- Rac1 GTPase, a multifunctional player in the regulation of genotoxic stress response.Cell cycle (Georgetown, Tex.) · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (γH2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGFβ, αSMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the γH2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGFβ, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging.
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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.