{"doi":"10.1016/j.bbadis.2023.166979","title":"TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction","abstract":null,"journal":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","year":2024,"id":655872,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1712088,"name":"Li-Guo Wang","orcid":null,"position":1,"is_corresponding":false},{"id":1329634,"name":"Lu Huang","orcid":"0009-0005-2530-569X","position":2,"is_corresponding":false},{"id":1712089,"name":"Yi-Fei Ren","orcid":null,"position":3,"is_corresponding":false},{"id":1712090,"name":"Zhen Ge","orcid":null,"position":4,"is_corresponding":false},{"id":1712091,"name":"Zuo-Ying Hu","orcid":null,"position":5,"is_corresponding":false},{"id":1276152,"name":"Jun-Jie Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":1712092,"name":"Shao-Liang Chen","orcid":null,"position":7,"is_corresponding":false},{"id":1712087,"name":"Guang-Feng Zuo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction","abstract":"Heart failure (HF) with preserved ejection fraction (HFpEF) is now the most common form of HF and has been reported to be closely related to diabetes. Accumulating evidence suggests that HFpEF patients exhibit cardiac fibrosis. This study investigates whether direct targeted inhibition of the activation of cardiac fibroblasts (CFs), the main effector cells in cardiac fibrosis, improves diabetes-induced HFpEF and elucidates the underlying mechanisms. Twenty-week-old db/db mice exhibited HFpEF, as confirmed by echocardiography and hemodynamic measurements. Proteomics was performed on CFs isolated from the hearts of 20-week-old C57BL/6 and db/db mice. Bioinformatic prediction was used to identify target proteins. Experimental validation was performed in both high glucose (HG)-treated neonatal mouse CFs (NMCFs) and diabetic hearts. TAX1 binding protein 1 (TAX1BP1) was identified as the most significantly differentially expressed protein between 20-week-old C57BL/6 and db/db mice. TAX1BP1 mRNA and protein were markedly downregulated in CFs from diabetic hearts and HG-cultured NMCFs. Overexpression of TAX1BP1 profoundly inhibited HG/diabetes-induced NF-κB nuclear translocation and collagen synthesis in CFs, improved cardiac fibrosis, hypertrophy, inflammation and HFpEF in diabetic mice. Mechanistically, signal transducer and activator of transcription 3 (STAT3), which is phosphorylated and translocated from the cytoplasm into the nucleus under hyperglycemic conditions, bound to TAX1BP1 promoter and blocked TAX1BP1 transcriptional activity, consequently promoting NF-κB nuclear translocation and collagen synthesis in CFs, aggravating cardiac fibrosis, hypertrophy and inflammation, leading to HFpEF in db/db mice. Taken together, our findings demonstrate that targeting regulation of STAT3-TAX1BP1-NF-κB signaling in CFs may be a promising therapeutic approach for diabetes-induced HFpEF.","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38065272","pmcid":null,"openalex_id":"https://openalex.org/W4389410274","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82170350","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82170363","title":null}],"total_grants":2,"fwci":0.7132,"citation_percentile":0.74148592,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2026,"count":2}],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0925443923003459?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0925443923003459?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbadis.2023.166979","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38065272","host_type":"repository"}],"fields_of_study":["Cardiac Fibrosis and Remodeling","Signaling Pathways in Disease","NF-κB Signaling Pathways"],"mesh_terms":["Animals","Collagen","Diabetes Mellitus, Experimental","Fibroblasts","Fibrosis","Heart Failure","Humans","Hypertrophy","Inflammation","Mice, Inbred C57BL","Cardiomyopathies","Neoplasm Proteins","Stroke Volume","Down-Regulation","NF-kappa B","Intracellular Signaling Peptides and Proteins","STAT3 Transcription Factor","Mice"],"keywords":["Heart failure","Heart failure with preserved ejection fraction","Fibrosis","Ejection fraction","Downregulation and upregulation","Diabetes mellitus","Medicine","Cardiac fibrosis","Internal medicine","Endocrinology","Inflammation","Diabetic cardiomyopathy","Muscle hypertrophy","Cardiology","Chemistry","Cardiomyopathy","Biochemistry","Stat3","Cardiac fibroblasts","Diabetes","Tax1bp1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T19:11:46.642819Z","pmid":null,"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":[]}