ArticleDrug design, development and therapy2020
KLF6 Induces Apoptosis in Human Lens Epithelial Cells Through the ATF4-ATF3-CHOP Axis.
Article in Drug design, development and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Dual regulation of Atf3 and Lonp1 as therapeutic targets in cerebral ischaemia-reperfusion injury.Stroke and vascular neurology · 2025Article
- Loss of alpha-kinase 1 contributes to the formation of congenital cataracts in mice.Cellular & molecular biology letters · 2025Article
- How transcription factors regulate apoptosis in endometriosis (Review).Molecular medicine reports · 2025Review
- Role of C/EBP Homologous Protein (CHOP) and Nupr1 Interaction in Endoplasmic Reticulum Stress-Induced Apoptosis of Lens Epithelial Cells.Molecular biotechnology · 2025Article
- TIGAR Suppresses ER Stress-Induced Neuronal Injury through Targeting ATF4 Signaling in Cerebral Ischemia/Reperfusion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Research Progress of Epigenetic Modifications in Myopia.International journal of medical sciences · 2025Review
- Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.Biomolecules · 2024Review
- CHOP regulated by METTL14-m6A affects cell cycle arrest and regorafenib sensitivity in HCC cells.BMC cancer · 2024Article
- Analysis of Toxic Effects of Fluoride on Ovine Follicular Granulosa Cells Using RNA-Seq.Antioxidants (Basel, Switzerland) · 2024Article
- A bibliometric and visualized analysis of the pathogenesis of cataracts from 1999 to 2023.Heliyon · 2024Article
- Glutamate is effective in decreasing opacity formed in galactose-induced cataract model.Scientific reports · 2024Article
- Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy.Journal of diabetes research · 2024Article
- Article
- MicroRNA-22-3p in human umbilical cord mesenchymal stem cell-secreted exosomes inhibits granulosa cell apoptosis by targeting KLF6 and ATF4-ATF3-CHOP pathway in POF mice.Apoptosis : an international journal on programmed cell death · 2023Article
- MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts.Translational vision science & technology · 2023Article
- New Insight into the Concanavalin A-Induced Apoptosis in Hepatocyte of an Animal Model: Possible Involvement of Caspase-Independent Pathway.Molecules (Basel, Switzerland) · 2023Article
- Ginsenoside Rh2 Induces HeLa Apoptosis through Upregulating Endoplasmic Reticulum Stress-Related and Downstream Apoptotic Gene Expression.Molecules (Basel, Switzerland) · 2022Article
- Senescence marker protein30 protects lens epithelial cells against oxidative damage by restoring mitochondrial function.Bioengineered · 2022Article
- The E3 Ligase RNF157 Inhibits Lens Epithelial Cell Apoptosis by Negatively Regulating p53 in Age-Related Cataracts.Investigative ophthalmology & visual science · 2022Article
- MiR-200c-3p aggravates gastric cell carcinoma via KLF6.Genes & genomics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany studies have confirmed that high myopia is related to the high prevalence of cataracts, which results from apoptosis of lens epithelial cells (LECs) due to endoplasmic reticulum stress. Krüppel-like factor 6 (KLF6) is a tumor suppressor that is involved in the regulation of cell proliferation and apoptosis. PURPOSE: In this study, our purpose was to find the relationship between KLF6-induced apoptosis in LECs and ATF4 (activating transcription factor 4)-ATF3 (activating transcription factor 3)-CHOP (C/EBP homologous protein) signaling pathway.
methodsKLF6, ATF4, ATF3, and CHOP were ectopically expressed using cDNAs subcloned into the pCDNA3.1+ vector. ATF4, ATF3, and CHOP knockdown were performed by small interfering RNA (siRNA). Expression of relative gene was tested using QT-PCR and western-blot. Then, accompanied by UVB stimulation, cell viability was measured by CCK-8 assay; The cell damage was examined by live & dead staining; The apoptotic markers Bax and Bcl-2 were detected by immunoblotting; Quantitative apoptotic levels were measured with the Apoptosis Detection Kit; The expression level of reactive oxygen-free radical (ROS) was analyzed by DCFH-DA` probe.
resultsEctopically expressed ATF4, ATF3, and CHOP-induced apoptosis in cells, whereas ATF4, ATF3, and CHOP knockdown by small interfering RNA (siRNA) blocked KLF6-induced apoptosis. In addition, we determined that ATF4 regulates ATF3 and CHOP expression and that ATF3 silencing reduces CHOP upregulation without changing ATF4 levels; however, ATF4 and ATF3 expression was unaffected by blockade of CHOP, suggesting that KLF6 triggers endoplasmic reticulum stress in LECs by mediating the ATF4-ATF3/CHOP axis. Besides, KLF6 overexpression significantly induced LEC apoptosis under UV radiation, as demonstrated by the elevated Bax/Bcl-2 ratio.
conclusionThe ATF4-ATF3-CHOP pathway plays an important role in KLF6-induced apoptosis in HLECs. Our results increase our understanding of the mechanisms that regulate LEC apoptosis and contribute to the development of a new preventative strategy for cataract.
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