ArticleJournal of molecular histology2019
Hyperinsulinemia-induced KLF5 mediates endothelial angiogenic dysfunction in diabetic endothelial cells.
Article in Journal of molecular histology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Silencing of OIP5-AS1 Protects Endothelial Cells From ox-LDL-Triggered Injury by Regulating KLF5 Expression via Sponging miR-135a-5p.Frontiers in cardiovascular medicine · 2021Pooled it
- Type 2 Diabetes Mellitus as a Multisystem Disease: From Insulin Resistance to Organ Crosstalk-A Narrative Review.Biomedicines · 2026Review
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Single cell and spatial characterization of the human pancreas reveals drivers of beta cell dysfunction in cystic fibrosis.bioRxiv : the preprint server for biology · 2025Article
- KLF5 drives granulosa cell apoptosis and inflammatory injury in polycystic ovary syndrome via transcriptional activation of TXNIP.In vitro cellular & developmental biology. Animal · 2025Article
- scDIFF: automatic cell type annotation using scATAC-seq data by incorporating bulk-level genomic and epigenomic information in a deep diffusive transformer.Briefings in bioinformatics · 2025Article
- α-Glucosidase Inhibition-Guided Network Pharmacology and Molecular Docking Reveal the Antidiabetic Potential ofInternational journal of molecular sciences · 2025Article
- Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities.Frontiers in cardiovascular medicine · 2024Review
- Participation of Krüppel-like Factors in Atherogenesis.Metabolites · 2023Review
- Mapping the cardiac vascular niche in heart failure.Nature communications · 2022Article
- Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.Journal of molecular and cellular cardiology · 2022Review
- Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies.Journal of molecular cell biology · 2021Review
- Roles of Krüppel-like factor 5 in kidney disease.Journal of cellular and molecular medicine · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reduced expression of endothelial nitric oxide synthase (eNOS) is a hallmark of endothelial dysfunction in diabetes, which predisposes diabetic patients to numerous cardiovascular complications including blunted angiogenesis. The Krüppel-like factor (KLF) five has been implicated as a central regulator of cardiovascular remodeling, but its role in endothelial cells (ECs) remains poorly understood. We show here that expression of endothelial KLF5 was significantly increased in the ECs from mouse diabetes mellitus type 2 (T2DM) model, when compared to non-diabetic or T1DM mouse. KLF5 up-regulation by insulin was dependent on activation of multiple pathways, including mammalian target of rapamycin, oxidative stress and Protein kinase C pathways. Hyperinsulinemia-induced KLF5 inhibited endothelial function and migration, and thereby compromised in vitro and in vivo angiogenesis. Mechanistically, KLF5 acted in concert with the MTA1 coregulator to negatively regulate NOS3 transcription, thereby leading to the diminished eNOS levels in ECs. Conversely, potentiation of cGMP content (the essential downstream effector of eNOS signaling) by pharmacological approaches successfully rescued the endothelial proliferation and in vitro tube formation, in the HUVECs overexpressing the exogenous KLF5. Collectively, the available data suggest that the augmentation of endothelial KLF5 expression by hyperinsulinemia may represent a novel mechanism for negatively regulating eNOS expression, and may thus help to explain for the T2DM-related endothelial dysfunction at the transcriptional level.
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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 OpenQuestion graph.