ArticleAmerican journal of physiology. Renal physiology2012
Loss of TIMP3 selectively exacerbates diabetic nephropathy.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Guidelines for measuring cardiac physiology in mice.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- MicroRNA-21 in glomerular injury.Journal of the American Society of Nephrology : JASN · 2015Trial
- Understanding the Roles of Non-coding RNAs and Exosomal Non-Coding RNAs in Diabetic Nephropathy.Current molecular medicine · 2025Review
- WTAP-mediated mRedox report : communications in free radical research · 2024Article
- Sirt1 activation prevents high glucose-induced angiotensin converting enzyme 2 downregulation in renal tubular cells by regulating the TIMP3/ADAM17 pathway.Molecular biology reports · 2024Article
- Exploring the genetic causal association of TIMP3 on CKD and kidney function: a two-sample mendelian randomization.Frontiers in genetics · 2024Article
- Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system.JCI insight · 2023Article
- The Role of MicroRNA in the Pathogenesis of Diabetic Nephropathy.International journal of molecular sciences · 2023Review
- Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding.Membranes · 2022Review
- Long Non-Coding RNAs in the Pathogenesis of Diabetic Kidney Disease.Frontiers in cell and developmental biology · 2022Review
- TIMP3 involvement and potentiality in the diagnosis, prognosis and treatment of diabetic nephropathy.Acta diabetologica · 2021Review
- Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling.Diabetology & metabolic syndrome · 2021Article
- Angiotensin-converting enzyme 2 and kidney diseases in the era of coronavirus disease 2019.The Korean journal of internal medicine · 2021Review
- Restoration of renal TIMP3 levels via genetics and pharmacological approach prevents experimental diabetic nephropathy.Clinical and translational medicine · 2021Article
- Overexpression of Linc 4930556M19Rik Suppresses High Glucose-Triggered Podocyte Apoptosis, Fibrosis and Inflammation via the miR-27a-3p/Metalloproteinase 3 (TIMP3) Axis in Diabetic Nephropathy.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Epigenetic Alterations Are Associated With Gastric Emptying Disturbances in Diabetes Mellitus.Clinical and translational gastroenterology · 2020Observational
- Matrix Metalloproteinases in Diabetic Kidney Disease.Journal of clinical medicine · 2020Review
- ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19.Frontiers in immunology · 2020Review
- LncRNA TUG1 ameliorates diabetic nephropathy by inhibiting miR-21 to promote TIMP3-expression.International journal of clinical and experimental pathology · 2019Article
- Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic?American journal of physiology. Renal physiology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetic nephropathy is the most common cause of end-stage renal disease. Polymorphism in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene, and the ECM-bound inhibitor of matrix metalloproteinases (MMPs), has been linked to diabetic nephropathy in humans. To elucidate the mechanism, we generated double mutant mice in which the TIMP3 gene was deleted in the genetic diabetic Akita mouse background. The aggravation of diabetic injury occurred in the absence of worsening of hypertension or hyperglycemia. In fact, myocardial TIMP3 levels were not affected in Akita hearts, and cardiac diastolic and systolic function remained unchanged in the double mutant mice. However, TIMP3 levels increased in Akita kidneys and deletion of TIMP3 exacerbated the diabetic renal injury in the Akita mouse, characterized by increased albuminuria, mesangial matrix expansion, and kidney hypertrophy. The progression of diabetic renal injury was accompanied by the upregulation of fibrotic and inflammatory markers, increased production of reactive oxygen species and NADPH oxidase activity, and elevated activity of TNF-α-converting enzyme (TACE) in the TIMP3(-/-)/Akita kidneys. Moreover, while the elevated phospho-Akt (S473 and T308) and phospho-ERK1/2 in the Akita mice was not detected in the TIMP3(-/-)/Akita kidneys, PKCβ1 (but not PKCα) was markedly elevated in the double mutant kidneys. Our data provide definitive evidence for a critical and selective role of TIMP3 in diabetic renal injury consistent with gene expression findings from human diabetic kidneys.
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Registered trials
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