ArticleRedox biology2019
S-nitrosation impairs KLF4 activity and instigates endothelial dysfunction in pulmonary arterial hypertension.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Mechanism of KLF4-Mediated NF-κB/NLRP3 Pathway Regulating Arteriovenous Fistula Dysfunction.Acta Cardiologica Sinica · 2026Article
- KLF4 Protects Against Sepsis-Induced Coagulopathy via Inhibition of the AKT/mTOR/STAT3 Signaling Pathway.Journal of inflammation research · 2026Article
- Identification of novel biomarkers and drug targets for frailty-related skeletal muscle aging: a multi-omics study.QJM : monthly journal of the Association of Physicians · 2025Article
- KLF4 interacts with TXNIP to modulate the pyroptosis in ulcerative colitis via regulating NLRP3 signaling.Immunity, inflammation and disease · 2024Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- Insights into Endothelin Receptors in Pulmonary Hypertension.International journal of molecular sciences · 2023Review
- Protective role of zinc in the pathogenesis of respiratory diseases.European journal of clinical nutrition · 2023Review
- Participation of Krüppel-like Factors in Atherogenesis.Metabolites · 2023Review
- Effect of the FA2H Gene on cashmere fineness of Jiangnan cashmere goats based on transcriptome sequencing.BMC genomics · 2022Article
- Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension.Molecules (Basel, Switzerland) · 2022Review
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- FGF21 attenuates hypoxia‑induced dysfunction and inflammation in HPAECs via the microRNA‑27b‑mediated PPARγ pathway.International journal of molecular medicine · 2021Article
- Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis-Nitro-Redox Interconnections.Antioxidants (Basel, Switzerland) · 2021Review
- Endogenous sulfur dioxide is a novel inhibitor of hypoxia-induced mast cell degranulation.Journal of advanced research · 2021Article
- Endothelial Cell-Derived SOOxidative medicine and cellular longevity · 2021Article
- Epigallocatechin-3-Gallate (EGCG), an Active Compound of Green Tea Attenuates Acute Lung Injury Regulating Macrophage Polarization and Krüpple-Like-Factor 4 (KLF4) Expression.Molecules (Basel, Switzerland) · 2020Article
- Combination of Dichloroacetate and Atorvastatin Regulates Excessive Proliferation and Oxidative Stress in Pulmonary Arterial Hypertension Development via p38 Signaling.Oxidative medicine and cellular longevity · 2020Article
- Novel Regulators and Targets of Redox Signaling in Pulmonary Vasculature.Current opinion in physiology · 2019Article
- Overexpression of Krüppel-Like Factor 4 Suppresses Migration and Invasion of Non-Small Cell Lung Cancer Through c-Jun-NH2-Terminal Kinase/Epithelial-Mesenchymal Transition Signaling Pathway.Frontiers in pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Krüppel-like factor 4 (KLF4) is a transcription factor with conserved zinc finger domains. As an essential regulator of vascular homeostasis, KLF4 exerts a protective effect in endothelial cells (ECs), including regulating vasodilation, inflammation, coagulation and oxidative stress. However, the underlying mechanisms modifying KLF4 activity in mediating vascular function remain poorly understood. Recently, essential roles for S-nitrosation have been implicated in many pathophysiologic processes of cardiovascular disease. Here, we demonstrated that KLF4 could undergo S-nitrosation in response to nitrosative stress in ECs, leading to the decreased nuclear localization with compromised transactivity. Mass-spectrometry and site-directed mutagenesis revealed that S-nitrosation modified KLF4 predominantly at Cys437. Functionally, KLF4 dependent vasodilatory response was impaired after S-nitrosoglutathione (GSNO) treatment. In ECs, endothelin-1 (ET-1) induced KLF4 S-nitrosation, which was inhibited by an endothelin receptor antagonist Bosentan. In hypoxia-induced rat model of pulmonary arterial hypertension (PAH), S-nitrosated KLF4 (SNO-KLF4) was significantly increased in lung tissues, along with decreased nuclear localization of KLF4. In summary, we demonstrated that S-nitrosation is a novel mechanism for the post-translational modification of KLF4 in ECs. Moreover, these findings suggested that KLF4 S-nitrosation may be implicated in the pathogenesis of vascular dysfunction and diseases such as PAH.
Indexed as
Identifiers
What OpenQuestion holds
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.