{"doi":"10.1016/j.redox.2020.101692","title":"In vivo AAV delivery of glutathione reductase gene attenuates anti-aging gene klotho deficiency-induced kidney damage","abstract":"Klotho is an aging-suppressor gene which leads to accelerated aging when disrupted. This study was designed to investigate whether glutathione reductase (GR), a critical intracellular antioxidant enzyme, is involved in the pathogenesis of kidney damages associated with accelerated aging in Klotho-haplodeficient (KL+/–) mice. Klotho-haplodeficient (KL+/–) mice and WT mice were used. We found that Klotho haplodeficiency impaired kidney function as evidenced by significant increases in plasma urea and creatinine and a decrease in urinary creatinine in KL+/– mice. The expression and activity of GR was decreased significantly in renal tubular epithelial cells of KL+/– mice, suggesting that Klotho deficiency downregulated GR. We constructed adeno-associated virus 2 (AAV2) carrying GR full-length cDNA (AAV-GR). Interestingly, in vivo AAV-GR delivery significantly improved Klotho deficiency-induced renal functional impairment and structural remodeling. Furthermore, in vivo expression of GR rescued the downregulation of the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, which subsequently diminished oxidative damages in kidneys, as evidenced by significant decreases in renal 4-HNE expression and urinary 8-isoprostane levels in KL mice. This study provides the first evidence that Klotho deficiency-induced kidney damage may be partly attributed to downregulation of GR expression. In vivo delivery of AAV-GR may be a promising therapeutic approach for aging-related kidney damage.","journal":"Redox Biology","year":2020,"id":63935,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337938,"name":"Shirley Wang","orcid":"0000-0002-9580-6693","position":1,"is_corresponding":false},{"id":11105,"name":"Yi Lin","orcid":"0000-0002-1556-6416","position":2,"is_corresponding":false},{"id":289919,"name":"Zhongjie Sun","orcid":"0000-0001-6599-1405","position":3,"is_corresponding":false},{"id":338621,"name":"Diansa Gao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T21:11:24.000992Z","pmid":"32863229","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}