Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability

Nie, He-zhong-rong; Zhou, Yi-wen; Yu, Xiao-hong; Yin, Cong-guo; Li, Ling-fei; Hao, Hui-qin; Yuan, Tao; Pan, Yong

doi:10.1038/s41401-024-01238-3

Cited by 4 publications

(1 citation statement)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We further found that miR-146a-5p regulates the JNK signaling pathway. KLF4, a critical transcription factor, is predicted to control multiple immune responses [32][33][34][35]. Similarly, in our study, we found that the expression of KLF4 in macrophage was signi cantly inhibited by exosomes from LPS-activated HSCs with high miR-146a-5p expression.…”

Section: Discussionsupporting

confidence: 80%

Exosomal miR-146a-5p Derived from HSCs Accelerates Sepsis-induced Liver Injury by Suppressing KLF-4

Sheng,

Song,

Gao

et al. 2024

Preprint

View full text Add to dashboard Cite

Background This study aims to investigate whether and how LPS-activated hepatic stellate cells (HSCs) could regulate macrophage activity, as well as to explore the impact of microRNA(miRNA) in exosomes from HSCs in this process. Methods Mice subjected to lipopolysaccharide (LPS) or Cecal Ligation and Puncture (CLP) were used to explore sepsis-induced liver injury. Liver injury was evaluated by HE staining, and AST and ALT levels were measured. LPS-Exo or N-LPS-Exo from HSCs were added to hepatic macrophages, and the expression of iNOS, IL-1β, and TNF-α was detected by Western Blotting. miRNA microarray analysis and PCR were used to evaluate differentially expressed miRNAs between LPS-Exo and N-LPS-Exo. Target genes were screened using the TargetScan database and verified by luciferase assays and WB. Inflammation and macrophage activity were observed in vivo by HE and CD86 staining in mice injected with PKH67-labeled LPS-Exo or N-LPS-Exo. Results Sepsis-related liver injury activates hepatic stellate cells, which regulate macrophage activity through exosomes. Specifically, exosomal miR-146a-5p secreted by hepatic stellate cells targets KLF-4, regulating the macrophage inflammatory response via the JNK signaling pathway. Conclusion Exosomes containing miRNA-146a-5p released from HSCs following LPS treatment may increase macrophage sensitivity to LPS and trigger an inflammatory response. Exosomal miR-146a-5p derived from HSCs accelerates sepsis-induced liver injury by suppressing KLF-4 expression.

show abstract

Section: Discussionsupporting

confidence: 80%

Exosomal miR-146a-5p Derived from HSCs Accelerates Sepsis-induced Liver Injury by Suppressing KLF-4

Sheng,

Song,

Gao

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Krüppel‐like factors family in health and disease

Xiang,

Yang,

Deng

et al. 2024

MedComm

View full text Add to dashboard Cite

Krüppel‐like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C‐terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family.

show abstract

Evidence further linking the intestine to cardiovascular disease

Sulaiman,

Reddy,

Fogelman

2024

Current Opinion in Lipidology

View full text Add to dashboard Cite

Purpose of review To review recent publications linking the intestine to cardiovascular disease. Recent findings Aromatic amino acid-derived metabolites produced by gut-bacteria were identified that increased or decreased the risk of cardiovascular events. Dietary phenylalanine was metabolized to phenylacetic acid by gut microbes, and converted into phenylacetylglutamine by the host, which increased thrombosis potential via adrenergic receptors and was associated with increased major adverse cardiovascular events. Another microbiota-associated metabolite of aromatic amino acids, indole-3-propionic acid, protected against heart failure with preserved ejection fraction. The mechanism by which dietary cholesterol is absorbed was found to involve the Nieman–Pick C1-like1 protein working together with a newly discovered protein called Aster. Levels of gut-derived bacterial lipopolysaccharide in serum that are an order of magnitude less than those seen in gram negative sepsis were shown to play a role in enhancing atherosclerosis and thrombosis. Summary Promising new therapeutic targets in the intestine for preventing or treating cardiovascular disease have been identified.

show abstract

Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability

Cited by 4 publications

References 29 publications

Exosomal miR-146a-5p Derived from HSCs Accelerates Sepsis-induced Liver Injury by Suppressing KLF-4

Exosomal miR-146a-5p Derived from HSCs Accelerates Sepsis-induced Liver Injury by Suppressing KLF-4

Krüppel‐like factors family in health and disease

Evidence further linking the intestine to cardiovascular disease

Contact Info

Product

Resources

About