ArticleJournal of translational medicine2022
The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 23 citations in OpenAlex.
- Keratin 18 functions as a lactyltransferase to trigger necroptosis in diabetic kidney disease by modulating Fas transcription.Experimental & molecular medicine · 2026Article
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation.Nature communications · 2026Article
- AARS1-mediated lactylation of H3K18 and STAT1 promotes ferroptosis in diabetic nephropathy.Cell death and differentiation · 2026Article
- Endothelial-to-mesenchymal transition in atherosclerosis: mechanisms, therapeutic targets, and future perspectives.Frontiers in cell and developmental biology · 2026Review
- Betulinic acid as a novel AT1R inhibitor: attenuation of liver fibrosis via modulation of endothelial-mesenchymal transition in chronic hepatic injury.Journal of translational medicine · 2025Article
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- A BACH1 inhibitor ameliorates myocardial infarction and limb ischemia in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- IGFBP5 promotes EndoMT and renal fibrosis through H3K18 lactylation in diabetic nephropathy.Cellular and molecular life sciences : CMLS · 2025Article
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- High-altitude hypoxia aggravated neurological deficits in mice induced by traumatic brain injury via BACH1 mediating astrocytic ferroptosis.Cell death discovery · 2025Article
- Broadening horizons: molecular mechanisms and disease implications of endothelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2025Review
- Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.Acta pharmacologica Sinica · 2024Article
- BACH1 controls hepatic insulin signaling and glucose homeostasis in mice.Nature communications · 2023Article
- SETD8 inhibits ferroptosis in pancreatic cancer by inhibiting the expression of RRAD.Cancer cell international · 2023Article
- Endothelial-to-mesenchymal transition: An underappreciated mediator of diabetic complications.Frontiers in endocrinology · 2023Review
- KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect.International journal of molecular sciences · 2022Article
- Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice.Frontiers in endocrinology · 2022Article
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7 authors at 3 institutions in 1 country.
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Abstract
backgroundDiabetic nephropathy (DN), the most common microvascular complication in patients with diabetes, induces kidney failure. Previous research showed that endothelial-to-mesenchymal transition (EndMT) of human glomerular endothelial cells (HGECs) is involved in the progression of DN. Moreover, SET domain-containing protein 8 (SETD8), ETS-domain containing protein (ELK1) and BTB and CNC homology 1 (bach1) all participate in endothelial injury. In this study, we hypothesize that the SETD8/ELK1/bach1 functional axis is involved in mediating EndMT in diabetic nephropathy.
methodsImmunohistochemistry, Western blotting and qPCR were performed to determine the protein and mRNA levels of genes in HGECs and the kidney tissues of participants and rats. Immunofluorescence, Co-IP and GST pulldown assays were performed to verify the direct interaction between SETD8 and ELK1. ChIP and dual-luciferase assays were performed to determine the transcriptional regulation of bach1 and Snail. AVV-SETD8 injection in rat kidney was used to verify the potential protective effect of SETD8 on DN.
resultsOur current study showed that hyperglycaemia triggered EndMT by increasing Snail expression both in vitro and in vivo. Moreover, high glucose increased bach1 expression in HGECs, positively regulating Snail and EndMT. As a transcription factor, ELK1 was augmented and participated in hyperglycaemia-induced EndMT via modulation of bach1 expression. Moreover, ELK1 was found to associate with SETD8. Furthermore, SETD8 negatively regulated EndMT by cooperating with bach1 to regulate Snail transcription. Furthermore, histone H4-Lys-20 monomethylation (H4K20me1), which is downstream of SETD8, was accompanied by ELK1 localization at the same promoter region of bach1. ELK1 overexpression enhanced bach1 promoter activity, which disappeared after specific binding site deletion. Mutual inhibition between ELK1 and SETD8 was found in HGECs. In vivo, SETD8 overexpression decreased ELK1 and bach1 expression, as well as EndMT. Moreover, SETD8 overexpression improved the renal function of rats with DN.
conclusionsSETD8 cooperates with ELK1 to regulate bach1 transcription, thus participating in the progression of DN. In addition, SETD8 interacts with bach1 to modulate Snail transcription, thus inducing EndMT in DN. SETD8 plays a core role in the SETD8/ELK1/bach1 functional axis, which participates in hyperglycaemia-mediated EndMT in DN, and SETD8 may be a potential therapeutic target for DN. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548.
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