ArticleCell research2019
Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 104 citations in OpenAlex.
- tRNA‑derived RNAs in hepatic diseases: From biological functions to clinical translation (Review).International journal of molecular medicine · 2026Review
- tRNA-derived small RNAs in tumor microenvironment remodeling: From mechanistic insights to therapeutic perspectives.Oncogene · 2026Review
- 5'tRF-GlyGCC Promotes Breast Cancer Progression via LDHA-Mediated Glycolysis and Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- tRNA-derived fragments (tRFs) as key non-coding players in the tumor transcriptome of colorectal cancer: introducing a new suspect responsible for the remaining unknowns of tumor pathology.Medical oncology (Northwood, London, England) · 2025Review
- The Hepatoprotective Properties of the Revised Formulation of Dahuang Xiaoshi Tang, an Ancient Chinese Herbal Decoction, Are Probed by Integrated Metabolomics and Network Pharmacology.Pharmaceuticals (Basel, Switzerland) · 2025Article
- NSun2-Mediated tsRNAs Alleviate Liver Fibrosis via FAK Dephosphorylation.Cell proliferation · 2025Article
- The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.Journal of advanced research · 2025Review
- A novel tsRNA signature -tRF-58:76-Tyr-GTA-2-M3 as potential biomarker and therapeutic target for duodenal atresia.Cell biology and toxicology · 2025Article
- Identification of tRF-29-79MP9P9NH525 as a biomarker and tumor suppressor of gastric cancer via regulating KIF14/AKT pathway.Cell death discovery · 2025Article
- tRNA-derived small RNAs in digestive tract diseases: Progress and perspectives.Genes & diseases · 2025Review
- Research progress on the roles of complement in liver injury.World journal of hepatology · 2025Review
- Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.Journal of translational medicine · 2025Article
- Food plants as adjuvant medicines: a review of protective effects and clinical potential in alcoholic liver disease.Frontiers in pharmacology · 2025Review
- Unveiling the hidden world of transfer RNA-derived small RNAs in inflammation.Journal of inflammation (London, England) · 2024Review
- Article
- Small non-coding RNA signatures in atrial appendages of patients with atrial fibrillation.Journal of cellular and molecular medicine · 2024Article
- Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.JCI insight · 2024Article
- Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers.Genes & diseases · 2024Review
- Review
- Curcumin improves atrial fibrillation susceptibility by regulating tsRNA expression in aging mouse atrium.PeerJ · 2024Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Complement is known to play a role in alcoholic fatty liver disease (AFLD), but the underlying mechanisms are poorly understood, thereby constraining the development of a rational approach for therapeutic intervention in the complement system. C3 deficiency has been shown to impart protective effects against ethanol-induced hepatic steatosis and inflammation. Here we demonstrate a protection effect in wild-type mice by treatment with CR2-Crry, a specific inhibitor of C3 activation. The expression of glycine transfer (t) RNA-derived fragments (Gly-tRFs) is upregulated in ethanol-fed mice and inhibition of Gly-tRFs in vivo decreases chronic ethanol feeding-induced hepatosteatosis without affecting inflammation. The expression of Gly-tRF was downregulated in C3-deficient or CR2-Crry-treated mice, but not in C5-deficient mice; Gly-tRF expression was restored by the C3 activation products C3a or Asp (C3a-des-Arg) via the regulation of CYP2E1. Transcriptome profiling of hepatic tissues showed that Gly-tRF inhibitors upregulate the expression of sirtuin1 (Sirt1) and subsequently affect downstream lipogenesis and β-oxidation pathways. Mechanistically, Gly-tRF interacts with AGO3 to downregulate Sirt1 expression via sequence complementarity in the 3' UTR. Notably, the expression levels of C3d, CYP2E1 and Gly-tRF are upregulated, whereas Sirt1 is decreased in AFLD patients compared to healthy controls. Collectively, our findings suggest that C3 activation products contribute to hepatosteatosis by regulating the expression of Gly-tRF. Complement inhibition at the C3 activation step and treatment with Gly-tRF inhibitors may be potential and precise therapeutic approaches for AFLD.
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