{"doi":"10.1152/ajprenal.00316.2007","title":"Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury","abstract":"<jats:p>Diabetic nephropathy is the most common cause of end-stage renal failure in the United States. Hyperglycemia is an important factor in the pathogenesis of diabetic nephropathy. Hyperglycemia upregulates the expression of transforming growth factor-β (TGF-β), which stimulates extracellular matrix deposition in the kidney, contributing to the development of diabetic nephropathy. Our previous studies demonstrated that the transcription factor, upstream stimulatory factor 2 (USF2), was upregulated by high glucose, which bound to an 18-bp sequence in the thrombospondin 1 (TSP1) gene promoter and regulated high glucose-induced TSP1 expression and TGF-β activity in mesangial cells, suggesting that USF2 might play a role in the development of diabetic nephropathy. In the present studies, we examined the effect of overexpression of USF2 on the development of diabetic nephropathy. Type 1 diabetes was induced in USF2 transgenic mice [USF2 (Tg)] and their wild-type littermates (WT) by injection of streptozotocin. Four groups of mice were studied: control WT, control USF2 (Tg), diabetic WT, and diabetic USF2 (Tg). Mice were killed after 15 wk of diabetes onset. At the end of studies, control USF2 (Tg) mice (∼6 mo old) exhibited increased urinary albumin excretion. These mice also exhibited glomerular hypertrophy, accompanied by increased TSP1, active TGF-β, fibronectin accumulation in the glomeruli compared with control WT littermates. Type 1 diabetes onset further augmented the urinary albumin excretion and glomerular hypertrophy in the USF2 (Tg) mice. These findings suggest that overexpression of USF2 accelerates the development of diabetic nephropathy.</jats:p>","journal":"American Journal of Physiology-Renal Physiology","year":2007,"id":15774,"datarank":1.6319286834356155,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":1.1120682980156564,"self_endowment_contribution":0.519860385419959,"citer_contribution":1.1120682980156564,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":27,"citers_with_citation_signal":22,"citers_with_endowment":22,"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":119049,"name":"Lihua Shi","orcid":null,"position":1,"is_corresponding":false},{"id":119050,"name":"Shuxia Wang","orcid":null,"position":2,"is_corresponding":false},{"id":119048,"name":"Shu Liu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17881461","pmcid":null,"openalex_id":"https://openalex.org/W2157781136","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK081555","title":null}],"total_grants":1,"fwci":2.0844,"citation_percentile":0.86468753,"influential_citations":1,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2015,"count":1},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2019,"count":3},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/ajprenal.00316.2007","host_type":"publisher"},{"url":"https://doi.org/10.1152/ajprenal.00316.2007","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17881461","host_type":"repository"}],"fields_of_study":["Apelin-related biomedical research","Adenosine and Purinergic Signaling","Migraine and Headache Studies","Medicine","Biology","Albuminuria","Animals","Diabetes Mellitus, Experimental","Diabetes Mellitus, Type 1","Diabetic Nephropathies","Electrophoretic Mobility Shift Assay","Fibronectins","Hypertrophy","Kidney Glomerulus","Male","Mice","Mice, Transgenic","Promoter Regions, Genetic","Thrombospondin 1","Time Factors","Transforming Growth Factor beta","Upstream Stimulatory Factors"],"mesh_terms":["Albuminuria","Animals","Diabetes Mellitus, Experimental","Diabetes Mellitus, Type 1","Diabetic Nephropathies","Fibronectins","Hypertrophy","Kidney Glomerulus","Male","Mice, Transgenic","Promoter Regions, Genetic","Time Factors","Transforming Growth Factor beta","Thrombospondin 1","Electrophoretic Mobility Shift Assay","Mice","Upstream Stimulatory Factors"],"keywords":["Upstream (networking)","Renal injury","Kidney","Internal medicine","Endocrinology","Medicine","Chemistry","Cancer research","Cell biology","Biology","Computer science","Computer network"],"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":"2026-06-01T18:54:05.419474Z","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":[]}