ArticleEMBO molecular medicine2013
Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Chinese herbal medicine and its active compounds in attenuating renal injuryFrontiers in endocrinology · 2023Pooled it
- MicroRNA-21 in glomerular injury.Journal of the American Society of Nephrology : JASN · 2015Trial
- Macrophage FOXO1 Inhibition Protects Against Hyperglycaemia-Associated Kidney Injury.Basic & clinical pharmacology & toxicology · 2026Article
- Hypoxia-Induced Metabolic Reprogramming and Markings of Cell Fate in Concentric Arterial Hypertrophy.bioRxiv : the preprint server for biology · 2025Article
- Influence of rsHealth science reports · 2025Article
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- Sorsby Fundus Dystrophy in an Asian Pedigree: Pathogenic Timp3 P.Y191c Variant Impairs Its Binding with Mmp2/9 and Cellular Localization.Clinical ophthalmology (Auckland, N.Z.) · 2025Article
- Inhibition of retinal neovascularization by Dendrobium polysaccharides: a review.Frontiers in pharmacology · 2025Review
- Integrative analysis of gene expression, protein abundance, and metabolomic profiling elucidates complex relationships in chronic hyperglycemia-induced changes in human aortic smooth muscle cells.Journal of biological engineering · 2024Article
- A proteomic atlas of kidney amyloidosis provides insights into disease pathogenesis.Kidney international · 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
- Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy.Journal of diabetes research · 2023Review
- Regulation of autophagy by natural polyphenols in the treatment of diabetic kidney disease: therapeutic potential and mechanism.Frontiers in endocrinology · 2023Review
- Differentially methylated and expressed genes in familial type 1 diabetes.Scientific reports · 2022Article
- Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding.Membranes · 2022Review
- The critical role of dysregulated autophagy in the progression of diabetic kidney disease.Frontiers in pharmacology · 2022Review
- TIMP3 involvement and potentiality in the diagnosis, prognosis and treatment of diabetic nephropathy.Acta diabetologica · 2021Review
- Identification and characterization of the mediator kinase-dependent myometrial stem cell phosphoproteome.F&S science · 2021Article
- ADAMs family in kidney physiology and pathology.EBioMedicine · 2021Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
ADAM17 and its inhibitor TIMP3 are involved in nephropathy, but their role in diabetic kidney disease (DKD) is unclear. Diabetic Timp3(-/-) mice showed increased albuminuria, increased membrane thickness and mesangial expansion. Microarray profiling uncovered a significant reduction of Foxo1 expression in diabetic Timp3(-/-) mice compared to WT, along with FoxO1 target genes involved in autophagy, while STAT1, a repressor of FoxO1 transcription, was increased. Re-expression of Timp3 in Timp3(-/-) mesangial cells rescued the expression of Foxo1 and its targets, and decreased STAT1 expression to control levels; abolishing STAT1 expression led to a rescue of FoxO1, evoking a role of STAT1 in linking Timp3 deficiency to FoxO1. Studies on kidney biopsies from patients with diabetic nephropathy confirmed a significant reduction in TIMP3, FoxO1 and FoxO1 target genes involved in autophagy compared to controls, while STAT1 expression was strongly increased. Our study suggests that loss of TIMP3 is a hallmark of DKD in human and mouse models and designates TIMP3 as a new possible therapeutic target for diabetic nephropathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.