ArticleJournal of cellular and molecular medicine2021
KLF4 down-regulation resulting from TLR4 promotion of ERK1/2 phosphorylation underpins inflammatory response in sepsis.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Epigenetic mechanism of HDAC5 in sepsis-induced acute intestinal injury through KLF4-mediated intestinal epithelial cell ferroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- ALK5 inhibition reduces HDM-induced inflammation and oxidative injury by regulating KLF4-mediated glycolysis in BEAS-2B cells.Journal of bioenergetics and biomembranes · 2026Article
- The AGO2-ATOX1 axis exacerbates inflammation in a mouse sepsis model.Central-European journal of immunology · 2026Article
- O‑GlcNAcylation: The crosstalk between infection immunity and autophagy in sepsis (Review).Molecular medicine reports · 2025Review
- Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Article
- KLF feedback loops in innate immunity.Frontiers in immunology · 2025Review
- Krüppel-like factor 4 control of immune cell function.Frontiers in immunology · 2025Review
- The role of KLF4 in phagocyte activation during infectious diseases.Frontiers in immunology · 2025Review
- Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.Frontiers in immunology · 2024Review
- Inhibition of miR-25 Ameliorates Cardiac Dysfunction and Fibrosis by Restoring Krüppel-like Factor 4 Expression.International journal of molecular sciences · 2023Article
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- [Effects of Krüppel-like factor 4 on inflammatory response and organ injury in septic mice].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Article
- Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.Genome biology · 2022Article
- KLF4 down-regulation resulting from TLR4 promotion of ERK1/2 phosphorylation underpins inflammatory response in sepsis.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis is a systemic inflammatory response to invading pathogens, leading to high mortality rates in intensive care units worldwide. Krüppel-like factor 4 (KLF4) is an important anti-inflammatory transcription factor. In this study, we investigate the anti-inflammatory role of KLF4 in caecal ligation and puncture (CLP)-induced septic mice and lipopolysaccharide (LPS)-induced RAW264.7 cells and its potential mechanism. We found that KLF4 was down-regulated in CLP-induced septic mice and in LPS-induced RAW264.7 cells, and that its overexpression led to increased survival rates of septic mice along with inhibited inflammatory response in vivo and in vitro. ITGA2B was up-regulated in the setting of sepsis and was inhibited by KLF4 overexpression. ITGA2B knock-down mimicked the effects of KLF4 overexpression on septic mice and LPS-induced RAW264.7 cells. TLR4 promoted the phosphorylation of ERK1/2 and then up-regulated the ubiquitination and the degradation of KLF4, thereby elevating the expression of ITGA2B. Moreover, TLR4 knock-down or treatment with PD98059 (a MEK inhibitor) inhibited inflammatory response in the setting of sepsis in vivo and in vitro. Furthermore, this effect of PD98059 treatment was lost upon KLF4 knock-down. Collectively, these results explain the down-regulation of KLF4 in sepsis, namely via TLR4 promotion of ERK1/2 phosphorylation, and identify ITGA2B as the downstream gene of KLF4, thus highlighting the anti-inflammatory role of KLF4 in sepsis.
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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.