KLF15

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2-/- mice...

Fasting leads to many physiological changes in peripheral tissues, including the liver, where suppression of de novo lipogenesis through inhibition of sterol regulatory element-binding protein 1 (SREBP-1) expression and/or activity is a key adaptation to preserve glucose for maintenance of blood glucose levels. Yoshinori Takeuchi and colleagues provide novel mechanistic insights into the regulation of SREBP-1 expression during fasting and highlight the importance of the hypothalamic-pituitary-adrenal axis and, particularly, glucocorticoid-induced binding of the glucocorticoid receptor to enhancer regions of the KLF15 (Kruppel-like factor 15) gene as a novel mechanism underlying the suppression of SREBP-1 during fasting...

Glioma is the most common primary malignancy of the central nervous system. Glioblastoma (GBM) has the highest degree of malignancy among the gliomas and the strongest resistance to chemotherapy and radiotherapy. Vasculogenic mimicry (VM) provides tumor cells with a blood supply independent of endothelial cells and greatly restricts the therapeutic effect of anti-angiogenic tumor therapy for glioma patients. Vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial cadherin (VE-cadherin) are currently recognized molecular markers of VM in tumors...

Sarcopenia is a progressive muscle disease characterized by the loss of skeletal muscle mass, strength, function, and physical performance. Since the disease code was assigned, attention has been focused on natural products that can protect against muscle atrophy. Cibotium barometz (Cibotium Rhizome) has been used as an herbal medicine for the treatment of bone or joint diseases in Asian countries. However, no studies have identified the mechanism of action of Cibotium Rhizome on muscle atrophy related to sarcopenia at the site of myotubes...

Acute kidney injury (AKI) is a common and serious disease with high morbidity and mortality, and its pathophysiological mechanisms are not fully understood. Increasing evidence suggests an important role of ferroptosis in AKI. Krüppel-like factor 15 (KLF15) is a transcription factor involved in several metabolic diseases, but its role in AKI and ferroptosis remains unclear. In this study, we explored the potential role of KLF15 using a folic acid-induced AKI model. Our study showed that KLF15 expression was reduced in kidney tissues of AKI mice, and KLF15 knockout exacerbated folic acid-induced ferroptosis and kidney injury...

PURPOSE: This study aims to identify key genes regulating tumor infiltrating plasma cells (PC) and provide new insights for innovative immunotherapy. METHODS: Key genes related to PC were identified using machine learning in lung adenocarcinoma (LUAD) patients. A prognostic model called PC scores was developed using TCGA data and validated with GEO cohorts. We assessed the molecular background, immune features, and drug sensitivity of the high PC scores group. Real-time PCR was utilized to assess the expression of hub genes in both localized LUAD patients and LUAD cell lines...

During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element-binding protein-1 (SREBP-1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting-induced Kruppel-like factor 15 (KLF15) with liver X receptor (LXR) serves as the essential mechanism for the nutritional regulation of SREBP-1 expression...

OBJECTIVE: To explore the role of branched-chain amino acid(BCAA) supplementation on muscle damage and the regulation of Krüppel-like factor 15(KLF15) and nuclear factor kappa B(NF-κB) mediated proteolytic pathways after an acute eccentric exercise. METHODS: Male SD rats were divided into placebo group(PLA) and BCAA group(BCAA) randomly, 32 rats per group. Both group were then placed into subgroups: placebo and pre-exercise group(PC), placebo and immediately after exercise group(PE), placebo and 6 h after exercise group(PE6), placebo and 12 h after exercise group(PE12), BCAA and pre-exercise group(BC), BCAA and immediately after exercise group(BE), BCAA and 6 h after exercise group(BE6), BCAA and 12 h after exercise group(BE12), 8 rats per group...

Successful muscle regeneration following injury is essential for functional homeostasis of skeletal muscles. Krüppel-like factor 15 (KLF15) is a metabolic transcriptional regulator in the muscles. However, little is known regarding its function in muscle regeneration. Here, we examined microarray datasets from the Gene Expression Omnibus (GEO) database, which indicated downregulated KLF15 in muscles from patients with various muscle diseases. Additionally, we found that Klf15 knockout (Klf15KO) impaired muscle regeneration following injury in mice...

Small ubiquitin-like modifier mediated modification (SUMOylation) is a critical post-translational modification that has a broad spectrum of biological functions, including genome replication and repair, transcriptional regulation, protein stability, and cell cycle progression. Perturbation or deregulation of a SUMOylation and deSUMOylation status has emerged as a new pathophysiological feature of lung diseases. In this review, we highlighted the link between SUMO pathway and lung diseases, especially the sumoylated substrate such as C/EBPα in bronchopulmonary dysplasia (BDP), PPARγ in pneumonia, TFII-I in asthma, HDAC2 in chronic obstructive pulmonary disease (COPD), KLF15 in hypoxic pulmonary hypertension (HPH), SMAD3 in idiopathic pulmonary fibrosis (IPF), and YTHDF2 in cancer...

OBJECTIVE: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles in mammalian cell differentiation and development. In this study, we investigated the function of KLF15 in the progression of osteoarthritis (OA). METHODS: 0Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male wild-type control (WT) mice and cartilage-specific KLF15 knockout (KO) mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining were performed...

BACKGROUND: This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer. METHODS: RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set...

The incidence of pulmonary fibrosis is on the rise, and existing treatments have limited efficacy in improving patient survival. The purpose of this study was to reveal the potential of Krüppel-like factor (KLF)15 activation in alleviating pulmonary fibrosis. Transforming growth factor beta (TGF-β) was utilized to induce lung fibroblasts to establish an in vitro model of pulmonary fibrosis. The impacts of TGF-β and KLF15 level on cell proliferation, migration, extracellular matrix (ECM) accumulation, and endoplasmic reticulum stress (ERS) were assessed...

Chronic stress leads to hypothalamic-pituitary-adrenal axis dysfunction, increasing cortisol levels. Glucocorticoids (GCs) promote muscle degradation and inhibit muscle synthesis, eventually causing muscle atrophy. In this study, we aimed to evaluate whether rice germ supplemented with 30% γ-aminobutyric acid (RG) attenuates muscle atrophy in an animal model of chronic unpredictable mild stress (CUMS). We observed that CUMS raised the adrenal gland weight and serum adrenocorticotropic hormone (ACTH) and cortisol levels, and these effects were reversed by RG...

Objective: To investigate the effects of aerobic intermittent exercise on the expressions of KLF15/mTOR related proteins to improve skeletal muscle lesions in type 2 diabetes rats. Methods: The experimental model of type 2 diabetes rats was established by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin (STZ). After modeling, rats were randomly divided into two groups: diabetes model group (DM), diabetes+exercise group (DE), and normal rats were set as control group (C), 10 rats in each group...

OBJECTIVE: Unexplained changes in regulation of branched chain amino acids (BCAA) during diabetes therapy with metformin have been known for years. Here we have investigated mechanisms underlying this effect. METHODS: We used cellular approaches, including single gene/protein measurements, as well as systems-level proteomics. Findings were then cross-validated with electronic health records and other data from human material. RESULTS: In cell studies, we observed diminished uptake/incorporation of amino acids following metformin treatment of liver cells and cardiac myocytes...

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Huosu-Yangwei (HSYW) in the treatment of advanced gastric cancer and chronic atrophic gastritis with precancerous lesions has been reported in clinical trials. However, the molecular mechanisms underlying its inhibition of gastric tumor are not well-understood. AIM OF THE STUDY: Combined with transcriptomics and systems network-based molecular mechanism to explore the potential circRNA-miRNA-mRNA network of HSYW in the treatment of gastric cancer...

Members of the Krüppel-like family of transcription factors are widely expressed, including in the kidney. Expression of some KLFs changes in acute kidney injury, and this may be adaptive or maladaptive, and result in effects on various cellular pathways. This mini-review will highlight the roles of KLF6 and KLF15 in control of proximal tubular cell metabolism.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have the potential to become powerful tools for disease modeling, drug testing, and transplantation; however, their immaturity limits their applications. Transcription factor (TF) overexpression can improve hPSC-CM maturity, but identifying these TFs has been elusive. Toward this, we establish here an experimental framework for systematic identification of maturation enhancing factors. Specifically, we performed temporal transcriptome RNAseq analyses of progressively matured hPSC-derived cardiomyocytes across 2D and 3D differentiation systems and further compared these bioengineered tissues to native fetal and adult-derived tissues...

Missense mutations in the DNA binding domain of p53 are characterized as structural or contact mutations based on their effect on the conformation of the protein. These mutations show gain-of-function activities, such as promoting increased metastatic incidence compared to p53 loss, often mediated by the interaction of mutant p53 with a set of transcription factors. These interactions are largely context specific. In order to understand the mechanisms by which p53 DNA binding domain mutations drive osteosarcoma progression, we created mouse models, in which either the p53 structural mutant p53R172H or the contact mutant p53R245W are expressed specifically in osteoblasts, yielding osteosarcoma tumor development...