ArticleJournal of the American Society of Nephrology : JASN2014
Tribbles homolog 3 attenuates mammalian target of rapamycin complex-2 signaling and inflammation in the diabetic kidney.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 39 citations in OpenAlex.
- Effects ofFrontiers in veterinary science · 2026Article
- Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.Emerging microbes & infections · 2024Article
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Cellular crosstalk of mesangial cells and tubular epithelial cells in diabetic kidney disease.Cell communication and signaling : CCS · 2023Review
- Single-cell transcriptomics: A new tool for studying diabetic kidney disease.Frontiers in physiology · 2022Review
- Article
- Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Tribbles homolog 3-mediated targeting the AKT/mTOR axis in mice with retinal degeneration.Cell death & disease · 2021Article
- Review
- A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals.PLoS genetics · 2020Article
- ADisease models & mechanisms · 2017Article
- Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases.Nature reviews. Nephrology · 2017Review
- Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.Scientific reports · 2017Article
- Enhanced Mandibular Bone Repair by Combined Treatment of Bone Morphogenetic Protein 2 and Small-Molecule Phenamil.Tissue engineering. Part A · 2017Article
- The Role of Endoplasmic Reticulum Stress in Diabetic Nephropathy.Current diabetes reports · 2017Review
- An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy.Nature communications · 2016Article
- Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.Stem cells translational medicine · 2016Article
- Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.Journal of clinical medicine · 2015Review
- mTOR contributes to ER stress and associated apoptosis in renal tubular cells.American journal of physiology. Renal physiology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The endoplasmic reticulum (ER) stress response is activated in the diabetic kidney and functions to reduce ER protein accumulation and improve cellular function. We previously showed that tribbles homolog 3 (TRB3), an ER stress-associated protein, is upregulated in the diabetic kidney. Here, we investigated whether absence of TRB3 alters outcomes in diabetic nephropathy. Type 1 diabetes was induced in TRB3 wild-type and knockout ((-/-)) mice by low-dose streptozotocin, and the mice were followed for 12 weeks. Diabetic TRB3(-/-) mice developed higher levels of albuminuria and increased expression of inflammatory cytokine and chemokine mRNA in renal cortices relative to wild-type littermates, despite similar hyperglycemia. Diabetic TRB3(-/-) mice also expressed higher levels of ER stress-associated molecules in both the renal cortices and glomeruli. This change was associated with higher renal cortical phosphorylation of AKT at serine 473 (Ser(473)), which is the AKT site phosphorylated by mammalian target of rapamycin complex-2 (mTORC2). We show in renal tubular cells that TRB3 binds to mTOR and the rapamycin-insensitive companion of mTOR (Rictor), a protein specific to mTORC2. Finally, we demonstrate in murine tubular cells that TRB3 can inhibit secretion of IL-6. Thus, TRB3 reduces albuminuria and inflammatory gene expression in diabetic kidney disease by a mechanism that may involve inhibition of the mTORC2/AKT pathway and may prove to be a novel therapeutic target.
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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 Socratic graph.