ArticleJournal of the American Society of Nephrology : JASN2013
Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK/STAT signaling.The Journal of clinical investigation · 2026Trial
- Everolimus-Involving Immunosuppression Attenuates Renal Interstitial Fibrosis Through Modulation of Mammalian Target of Rapamycin-Related Signal Transduction.International journal of molecular sciences · 2026Article
- Deubiquitinase USP7 stabilizes the histone demethylase KDM5B and promotes the progression of renal fibrosis through the TSC1/mTOR axis.Molecular biomedicine · 2026Article
- Cell-state- and compartment-dependent PI3K/Akt redox signaling in chronic kidney disease: mechanisms and translational implications.Frontiers in pharmacology · 2026Review
- mTOR blockade prevents progressive proteinuria but induces hyperglycaemia in obese Dahl salt-sensitive rats before puberty.Experimental physiology · 2025Article
- 4EBP1 phosphorylation mediates TGF-β1-induced hepatic fibrosis and upregulates HIF-1α expression.iScience · 2025Article
- Ras homolog enriched in brain 1 regulates β cell mass and β cell functionWorld journal of diabetes · 2025Article
- Spaceflight causes strain-dependent gene expression changes in the kidneys of mice.NPJ microgravity · 2025Article
- Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.Clinical and translational medicine · 2024Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis.JCI insight · 2023Article
- DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice.Nature communications · 2023Article
- New insights into fibrotic signaling in renal cell carcinoma.Frontiers in cell and developmental biology · 2023Review
- Transient expansion and myofibroblast conversion of adipogenic lineage precursors mediate bone marrow repair after radiation.JCI insight · 2022Article
- Ion channels as a therapeutic target for renal fibrosis.Frontiers in physiology · 2022Review
- Indoxyl Sulfate Contributes to mTORC1-Induced Renal Fibrosis via The OAT/NADPH Oxidase/ROS Pathway.Toxins · 2021Article
- Interleukin-7 Is Associated with Clinical and Pathological Activities in Immunoglobulin A Nephropathy and Protects the Renal Proximal Tubule Epithelium from Cellular Fibrosis.Current medical science · 2021Article
- Suppression of Allograft Fibrosis by Regulation of Mammalian Target of Rapamycin-Related Protein Expression in Kidney-Transplanted Recipients Treated with Everolimus and Reduced Tacrolimus.Annals of transplantation · 2021Article
- Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis.Frontiers in pharmacology · 2021Article
- Ufbp1, a Key Player of Ufm1 Conjugation System, Protects Against Ketosis-Induced Liver Injury via Suppressing Smad3 Activation.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras homolog enriched in brain (Rheb) is a small GTPase that regulates cell growth, differentiation, and survival by upregulating mammalian target of rapamycin complex 1 (mTORC1) signaling. The role of Rheb/mTORC1 signaling in the activation of kidney fibroblasts and the development of kidney fibrosis remains largely unknown. In this study, we found that Rheb/mTORC1 signaling was activated in interstitial myofibroblasts from fibrotic kidneys. Treatment of rat kidney interstitial fibroblasts (NRK-49F cell line) with TGFβ1 also activated Rheb/mTORC1 signaling. Blocking Rheb/mTORC1 signaling with rapamycin or Rheb small interfering RNA abolished TGFβ1-induced fibroblast activation. In a transgenic mouse, ectopic expression of Rheb activated kidney fibroblasts. These Rheb transgenic mice exhibited increased activation of mTORC1 signaling in both kidney tubular and interstitial cells as well as progressive interstitial renal fibrosis; rapamycin inhibited these effects. Similarly, mice with fibroblast-specific deletion of Tsc1, a negative regulator of Rheb, exhibited activated mTORC1 signaling in kidney interstitial fibroblasts and increased renal fibrosis, both of which rapamycin abolished. Taken together, these results suggest that Rheb/mTORC1 signaling promotes the activation of kidney fibroblasts and contributes to the development of interstitial fibrosis, possibly providing a therapeutic target for progressive renal disease.
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