{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yan Y"],"funding":["Fundamental Research Funds for the Central Universities","Huazhong Agricultural University Startup","National Key R&D Plan","Youth 1000 Plan Project"],"pagination":["494-504"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6495079"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16"],"pubmed_abstract":["MicroRNAs (miRNAs) act as regulators of aging at the tissue or organism level or as regulators of cellular senescence. Targeted deletion of miR-126 in mice causes partial embryonic lethality, but its biological function in the liver is still largely unknown. Here, we deleted miR-126a, using the CRISPR/Cas9 system in vitro and in vivo. miR-126a was reduced in the aging livers, and disruption of miR-126a in bone mesenchymal stem cells (BMSCs) induced age-associated telomere shortening, DNA damage responses, and proinflammatory cytokines. Moreover, disruption of miR-126a in mice caused hepatocyte senescence, inflammation, and metabolism deficiency. In addition, disruption of miR-126a via BMSC transplantation aggravated the severity of liver defects induced by cholestasis compared with that in the functional miR-126a BMSC group. Mechanistically, we identified versican (VCAN) as a novel direct miR-126a-5p target that induces telomere shortening, BMSC senescence, and nuclear factor κB (NF-κB) pathway activation. This study identified aging-related reduced expression of miR-126a and promotion of its target VCAN as a key mechanism in the regulation of hepatic metabolic function during aging and hepatic damage by inducing NF-κB pathway activation, DNA repair function disorder, and telomere attrition. The findings indicate that miR-126a may be a drug target for the treatment of hepatic failure."],"journal":["Molecular therapy. Nucleic acids"],"pubmed_title":["Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis."],"pmcid":["PMC6495079"],"funding_grant_id":["2017YFA0103202","2662017PY106","2662016PY087","2017YFA0103200","2662019YJ008"],"pubmed_authors":["Huang W","Huang X","Liu S","Wu D","Chen X","Zhang L","Yan Y","Qin D","Zhang C","Hu B","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis.","description":"MicroRNAs (miRNAs) act as regulators of aging at the tissue or organism level or as regulators of cellular senescence. Targeted deletion of miR-126 in mice causes partial embryonic lethality, but its biological function in the liver is still largely unknown. Here, we deleted miR-126a, using the CRISPR/Cas9 system in vitro and in vivo. miR-126a was reduced in the aging livers, and disruption of miR-126a in bone mesenchymal stem cells (BMSCs) induced age-associated telomere shortening, DNA damage responses, and proinflammatory cytokines. Moreover, disruption of miR-126a in mice caused hepatocyte senescence, inflammation, and metabolism deficiency. In addition, disruption of miR-126a via BMSC transplantation aggravated the severity of liver defects induced by cholestasis compared with that in the functional miR-126a BMSC group. Mechanistically, we identified versican (VCAN) as a novel direct miR-126a-5p target that induces telomere shortening, BMSC senescence, and nuclear factor κB (NF-κB) pathway activation. This study identified aging-related reduced expression of miR-126a and promotion of its target VCAN as a key mechanism in the regulation of hepatic metabolic function during aging and hepatic damage by inducing NF-κB pathway activation, DNA repair function disorder, and telomere attrition. The findings indicate that miR-126a may be a drug target for the treatment of hepatic failure.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2026-05-07T03:45:41.98Z","creation":"2025-05-18T12:51:13.738Z"},"accession":"S-EPMC6495079","cross_references":{"pubmed":["31051334"],"doi":["10.1016/j.omtn.2019.04.002"]}}