ArticleThe American journal of pathology2016
Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Extracellular Vesicles in Liver Fibrosis: Pathogenic Messengers, Diagnostic Biomarkers, and Therapeutic Nanovectors.Pharmaceutics · 2026Review
- Anti-CTGF/PD-1 bispecific antibody Y126S restrains desmoplastic and immunosuppressive microenvironment in pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- Enolase and 16.5-kDa Tegument-Associated Protein inJournal of extracellular biology · 2025Article
- Extracellular Vesicles and Micro-RNAs in Liver Disease.Seminars in liver disease · 2025Review
- Novel insights into the role of immunomodulatory extracellular vesicles in the pathogenesis of liver fibrosis.Biomarker research · 2024Review
- Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma.Cancers · 2024Review
- Formation and Investigation of Cell-Derived Nanovesicles as Potential Therapeutics against Chronic Liver Disease.Advanced healthcare materials · 2023Article
- Exosome-associated miRNA-99a-5p targeting BMPR2 promotes hepatocyte apoptosis during the process of hepatic fibrosis.Clinical and experimental medicine · 2023Article
- MicroRNAs and Nonalcoholic Steatohepatitis: A Review.International journal of molecular sciences · 2023Review
- Review
- Role of Extracellular Vesicles in Liver Diseases.Life (Basel, Switzerland) · 2023Review
- Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications.Frontiers in immunology · 2023Review
- [Effect of macrophage-derived exosomes on promoting hepatic stellate cell activation and platelet-derived growth factor expression].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Multifaceted roles of extracellular RNAs in different diseases.Military Medical Research · 2022Review
- M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model.iScience · 2022Article
- Article
- Circulating cell-specific extracellular vesicles as biomarkers for the diagnosis and monitoring of chronic liver diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Extracellular vesicles in inflammation: Focus on the microRNA cargo of EVs in modulation of liver diseases.Journal of leukocyte biology · 2022Review
- Review
- Diagnosis and Therapeutic Management of Liver Fibrosis by MicroRNA.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pathways of liver fibrosis are controlled by connective tissue growth factor (CCN2). In this study, CCN2 was identified as a target of miR-199a-5p, which was principally expressed in quiescent mouse hepatic stellate cells (HSCs) and directly suppressed production of CCN2. Up-regulated CCN2 expression in fibrotic mouse livers or in activated primary mouse HSCs was associated with miR-199a-5p down-regulation. MiR-199a-5p in quiescent mouse HSCs inhibited the activity of a wild-type CCN2 3' untranslated region (3'-UTR) but not of a mutant CCN2 3'-UTR lacking the miR-199a-5p-binding site. In activated mouse HSCs, CCN2, α-smooth muscle actin, and collagen 1(α1) were suppressed by a miR-199a-5p mimic, whereas in quiescent mouse HSCs, the inhibited CCN2 3'-UTR activity was blocked by a miR-199a-5p antagomir. CCN2 3'-UTR activity in human HSCs was reduced by a miR-199a-5p mimic. MiR-199a-5p was present at higher levels in exosomes from quiescent versus activated HSCs. MiR-199a-5p-containing exosomes were shuttled from quiescent mouse HSCs to activated mouse HSCs in which CCN2 3'-UTR activity was then suppressed. Exosomes from quiescent HSCs caused miR-199a-5p-dependent inhibition of CCN2, α-smooth muscle actin, or collagen 1(α1) in activated HSCs in vitro and bound to activated HSCs in vivo. Thus, CCN2 suppression by miR-199a-5p accounts, in part, for low-level fibrogenic gene expression in quiescent HSCs and causes dampened gene expression in activated HSCs after horizontal transfer of miR-199a-5p in exosomes from quiescent HSCs.
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