The role of KLF14 in multiple disease processes

Chen, Xiaoyan; Shi, Wenjie; Zhang, Heng

doi:10.1002/biof.1612

Cited by 26 publications

(41 citation statements)

References 57 publications

(133 reference statements)

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“…Moreover, KLF14 is a maternally expressed gene and has a large CpG island across most regions of the open reading frame (ORF). This CG-rich region regulates downstream gene expression and nuclear protein transcription by interacting with coactivators or immune complexes [ 10 ]. Previous studies have shown that KLF14 significantly regulates lipid metabolism and blood glucose levels, which are closely related to the pathogenesis of atherosclerosis, type 2 diabetes, insulin resistance, and other diseases [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

et al. 2022

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Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.

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Section: Introductionmentioning

confidence: 99%

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

et al. 2022

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“…KLF14 is associated with insulin resistance, dyslipidaemia, type 2 diabetes and a female-specific shift of body fat from gynoid to abdominal stores, in agreement with the hip-specific association in women found in our study. In mice, adipocyte-specific deletion of Klf14 results in similar metabolic effects, while Klf14 knockout results in spontaneous tumorigenesis 30 . TBX15 belongs to a family of transcription factors regulating differentiation, proliferation, tissue integrity and epithelial-mesenchymal transition, which are relevant to cancer development and metastasis 31 .…”

Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

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“…SH-SY5Y cells were first cultured in deoxygenated glucose-free DMEM medium using a hypoxic vessel maintained at 37°C for 4 h (95% N 2 and 5% CO 2 ). Then, the cells were transferred onto high glucose DMEM medium containing 10% FBS and cultured under normoxic conditions (5% CO 2 ) at 37°C for 24 h as previously described [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-532-5p protects against cerebral ischemia-reperfusion injury by directly targeting CXCL1

Shi

Zhao

et al. 2021

Aging

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We investigated the function of microRNA (miR)-532-5p in cerebral ischemia-reperfusion injury (CI/RI) and the underlying mechanisms using oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y cells and middle cerebral artery occlusion (MCAO) model rats. MiR-532-5p levels were significantly downregulated in OGD/R-treated SH-SY5Y cells and the brain tissues of MCAO model rats. MiR-532-5p overexpression significantly reduced apoptosis, reactive oxygen species (ROS), and inflammation in the OGD/R-induced SH-SY5Y cells. Bioinformatics analysis using the targetscan and miRDB databases as well as dual luciferase reporter assays confirmed that miR-532-5p directly binds to the 3’UTR of C-X-C Motif Ligand 1 (CXCL1). Methylation-specific PCR (MSP) analysis showed that miR-532-5p expression was reduced in OGD/R-treated SH-SY5Y cells because of miR-532-5p promoter hypermethylation. Moreover, 5-azacytidine, a methylation inhibitor, restored miR-532-5p expression in OGD/R-treated SH-SY5Y cells. Brain tissues of MCAO model rats showed significantly increased cerebral infarction areas, cerebral water, neuronal apoptosis, and activated CXCL1/CXCR2/NF-κB signaling, but these effects were alleviated by intraventricular injection of miR-532-5p agomir. These findings demonstrate that miR-532-5p overexpression significantly reduces in vitro and in vivo CI/RI by targeting CXCL1. Thus, miR-532-5p is a potential therapeutic target for patients with CI/RI.

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The role of KLF14 in multiple disease processes

Cited by 26 publications

References 57 publications

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

MicroRNA-532-5p protects against cerebral ischemia-reperfusion injury by directly targeting CXCL1

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