{"doi":"10.1016/j.redox.2020.101609","title":"Bone marrow deficiency of mRNA decaying protein Tristetraprolin increases inflammation and mitochondrial ROS but reduces hepatic lipoprotein production in LDLR knockout mice","abstract":"Tristetraprolin (TTP), an mRNA binding and decaying protein, plays a significant role in controlling inflammation by decaying mRNAs encoding inflammatory cytokines such as TNFalpha. We aimed to test a hypothesis that TTP in bone marrow (BM) cells regulates atherogenesis by modulating inflammation and lipid metabolism through the modulation of oxidative stress pathways by TTP target genes. In a BM transplantation study, lethally irradiated atherogenic LDLR−/− mice were reconstituted with BM cells from either wild type (TTP+/+) or TTP knockout (TTP−/−) mice, and fed a Western diet for 12 weeks. We made the following observations: (1) TTP−/− BM recipients display a significantly higher systemic and multi-organ inflammation than TTP+/+ BM recipients; (2) BM TTP deficiency modulates hepatic expression of genes, detected by microarray, involved in lipid metabolism, inflammatory responses, and oxidative stress; (3) TTP−/− BM derived macrophages increase production of mitochondrial reactive oxygen species (mtROS); (4) BM-TTP−/− mice display a significant reduction in serum VLDL/LDL levels, and attenuated hepatic steatosis compared to controls; and (5) Reduction of serum VLDL/LDL levels offsets the increased inflammation, resulting in no changes in atherosclerosis. These findings provide a novel mechanistic insight into the roles of TTP-mediated mRNA decay in bone marrow-derived cells in regulating systemic inflammation, oxidative stress, and liver VLDL/LDL biogenesis.","journal":"Redox Biology","year":2020,"id":76029,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"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":396949,"name":"Junfeng Wang","orcid":"0000-0001-9955-0659","position":1,"is_corresponding":false},{"id":396950,"name":"Stephen Iwanowycz","orcid":"0000-0002-2293-3309","position":2,"is_corresponding":false},{"id":396951,"name":"Yuzhen Wang","orcid":"0000-0003-1299-4519","position":3,"is_corresponding":false},{"id":396952,"name":"Diego Altomare","orcid":"0000-0002-9126-5703","position":4,"is_corresponding":false},{"id":237315,"name":"Ying Shao","orcid":"0000-0001-5879-0154","position":5,"is_corresponding":false},{"id":192287,"name":"Jianguo Liu","orcid":null,"position":6,"is_corresponding":false},{"id":376177,"name":"Perry J. Blackshear","orcid":"0000-0002-9561-8529","position":7,"is_corresponding":false},{"id":396953,"name":"Susan M. Lessner","orcid":"0000-0002-8409-5216","position":8,"is_corresponding":false},{"id":318652,"name":"E. Angela Murphy","orcid":"0000-0002-4803-5822","position":9,"is_corresponding":false},{"id":233134,"name":"Hong Wang","orcid":"0000-0001-6258-4070","position":10,"is_corresponding":false},{"id":233133,"name":"Xiaofeng Yang","orcid":"0000-0002-6854-6195","position":11,"is_corresponding":false},{"id":396954,"name":"Daping Fan","orcid":"0000-0002-4729-761X","position":12,"is_corresponding":false},{"id":239127,"name":"Fatma Saaoud","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T21:47:46.469293Z","pmid":"32591281","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":[]}