ArticleFrontiers in pharmacology2018
HDAC6 Inhibition Promotes Transcription Factor EB Activation and Is Protective in Experimental Kidney Disease.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Small bites for big problems: stepwise aggregate degradation by autophagy.Biochemical Society transactions · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Hyperosmotic Stress Promotes the Nuclear Translocation of TFEB in Tubular Epithelial Cells Depending on Intracellular CaCellular and molecular bioengineering · 2025Article
- Autophagy and Mitophagy in Diabetic Kidney Disease-A Literature Review.International journal of molecular sciences · 2025Review
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- Histone deacetylase 6 inhibition prevents hypercholesterolemia-induced erectile dysfunction independent of changes in markers of autophagy.Sexual medicine · 2024Article
- HDAC6 promotes inflammation in lupus nephritis mice by regulating transcription factors MAFF and KLF5 in renal fibrosis.Renal failure · 2024Article
- TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease.Renal failure · 2024Article
- The role of HDAC6 in enhancing macrophage autophagy via the autophagolysosomal pathway to alleviate legionella pneumophila-induced pneumonia.Virulence · 2024Article
- Quantifying Protein Acetylation in Diabetic Nephropathy from Formalin-Fixed Paraffin-Embedded Tissue.Proteomics. Clinical applications · 2024Article
- Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke.Current neuropharmacology · 2024Article
- Role of Histone Deacetylase 6 and Histone Deacetylase 6 Inhibition in Colorectal Cancer.Pharmaceutics · 2023Review
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Autophagy and mitophagy: physiological implications in kidney inflammation and diseases.American journal of physiology. Renal physiology · 2023Review
- The role of lysosomes in metabolic and autoimmune diseases.Nature reviews. Nephrology · 2023Review
- Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination.International journal of molecular sciences · 2023Review
- Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.The Journal of clinical investigation · 2023Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To contend with the deleterious effects of accumulating misfolded protein aggregates or damaged organelles cells rely on a system of quality control processes, among them the autophagy-lysosome pathway. This pathway is itself controlled by a master regulator transcription factor termed transcription factor EB (TFEB). When TFEB localizes to the cell nucleus it promotes the expression of a number of genes involved in protein clearance. Here, we set out to determine (1) whether TFEB expression is altered in chronic kidney disease (CKD); (2) whether inhibition of the cytosolic deacetylase histone deacetylase 6 (HDAC6) affects TFEB acetylation and nuclear localization; and (3) whether HDAC6 inhibition, in turn, alters the natural history of experimental CKD. TFEB mRNA and protein levels were observed to be diminished in the kidneys of humans with diabetic kidney disease, accompanied by accumulation of the protein aggregate adaptor protein p62 in tubule epithelial cells. In cultured NRK-52E cells, HDAC6 inhibition with the small molecule inhibitor Tubastatin A acetylated TFEB, increasing TFEB localization to the nucleus and attenuating cell death. In a rat model of CKD, Tubastatin A prevented the accumulation of misfolded protein aggregates in tubule epithelial cells, attenuated proteinuria progression, limited tubule cell death and diminished tubulointerstitial collagenous matrix deposition. These findings point to the common occurrence of dysregulated quality control processes in CKD and they suggest that TFEB downregulation may contribute to tubule injury in CKD. They also identify a regulatory relationship between HDAC6 and TFEB. HDAC6 inhibitors and TFEB activators both warrant further investigation as treatments for CKD.
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