Kruppel

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and the development of non-alcoholic steatohepatitis (NASH) might cause irreversible hepatic damage. Hyperlipidemia (HLP) is the leading risk factor for NAFLD. This study aims to illuminate the causative contributor and potential mechanism of Kallistatin (KAL) mediating HLP to NAFLD. 221 healthy control and 253 HLP subjects, 62 healthy control and 44 NAFLD subjects were enrolled. The plasma KAL was significantly elevated in HLP subjects, especially in hypertriglyceridemia (HTG) subjects, and positively correlated with liver injury...

UNLABELLED: Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Kruppel-like Factor 2 (KLF2) in the development of embryonically derived Large Cavity Macrophages (LCM) in the serous cavities. KLF2 not only directly regulates the transcription of genes previously shown to specify LCM identity, such as retinoic acid receptors and GATA6, but also is required for induction of many other transcripts that define the identity of these cells...

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet...

No abstract text is available yet for this article.

Poly ADP-ribose polymerase (PARP) inhibitor monotherapies are selectively effective in patients with pancreatic, breast, prostate, and ovarian cancers with BRCA1 mutations. Cancer patients with more frequent wild-type BRCA show poor responses to PARP inhibitors. Moreover, patients who are initially sensitive to these inhibitors eventually respond poorly to drugs. In the present study, we discover that abrogation of Kruppel-like factor 5 (KLF5) significantly inhibits homologous recombination, which is the main mechanism for DNA double-stranded repair...

Halloysite nanotubes (HNTs) are nanomaterials (NMs) derived from natural clays and have been considered as biocompatible NMs for biomedical uses. However, the cardiovascular toxicity of HNTs has not been thoroughly investigated. In this study, we compared the cardiotoxicity of HNTs and multi-walled carbon nanotubes (MWCNTs), focusing on the changes in Kruppel-like factor (KLF)-mediated signaling pathways. Mice were intravenously injected with 50 µg NMs, once a day, for 5 days, and then mouse hearts were removed for experiments...

BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke. OBJECTIVES: This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH. METHODS: The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed...

OBJECTIVES: A zinc-finger transcription factor family comprising specificity proteins (SPs) and Krüppel-like factor proteins (KLFs) plays an important role in dentin development and regeneration. However, a systematic regulatory network involving SPs/KLFs in odontoblast differentiation has not yet been described. This review examined the expression patterns of SP/KLF gene family members and their current known functions and mechanisms in odontoblast differentiation, and discussed prospective research directions for further exploration of mechanisms involving the SP/KLF gene family in dentin development...

Iron overload is associated with brain edema in the context of intracerebral hemorrhage (ICH). Here, we investigated the role of histone deacetylase 1 (HDAC1) in mediating oxidative damage induced by iron overload after ICH. Utilizing ICH mouse models and FeCl2 -induced HT-22 cell models, we assessed HDAC1 expression and its impact on iron overload and oxidative damage. We examined the levels of Kruppel like factor 4 (KLF4), RAN binding protein 9 (RANBP9), as well as the acetylation levels of HDAC1 and histones H3 and H4 in the KLF4 promoter, and the KLF4 level in the RANBP9 promoter...

No abstract text is available yet for this article.

Hepatic stellate cells (HSCs) are critical regulator contributing to the onset and progression of liver fibrosis. Chronic liver injury triggers HSCs to undergo vast changes and trans-differentiation into a myofibroblast HSCs, the mechanism remains to be elucidated. This study investigated that the involvement of hydroxymethylase TET1 (ten-eleven translocation 1) in HSC activation and liver fibrosis. It is revealed that TET1 levels were downregulated in the livers in mouse models of liver fibrosis and patients with cirrhosis, as well as activated HSCs in comparison to quiescent HSCs...

Lung cancer is a harmful type of malignancy and the leading cause of cancer-associated mortality. It is therefore imperative to develop novel drugs effective for treating this cancer. The Traditional Chinese Medicine compound Britannin has been previously reported to inhibit the development of certain cancers, such as pancreatic, breast and liver cancer. Moreover, Kruppel-like factor 5 (KLF5) has been identified an on oncogene in lung cancer. In the present study, the possible regulatory effects and underlying mechanism of Britannin in lung cancer were investigated...

Microglia-mediated neuroinflammation plays a critical role in the occurrence and progression of Alzheimer's disease (AD). In recent years, studies have increasingly explored microRNAs as biomarkers and treatment interventions for AD. This study identified a novel microRNA termed miR-25802 from our high-throughput sequencing dataset of an AD model and explored its role and the underlying mechanism. The results confirmed the miRNA properties of miR-25802 based on bioinformatics and experimental verification. Expression of miR-25802 was increased in the plasma of AD patients and in the hippocampus of APP/PS1 and 5 × FAD mice carrying two and five familial AD gene mutations...

Metastasis remains a major cause of morbidity and mortality in men with prostate cancer, and the functional impact of the genetic alterations, alone or in combination, driving metastatic disease remains incompletely understood. The proto-oncogene c-MYC, commonly deregulated in prostate cancer. Transgenic expression of c-MYC is sufficient to drive the progression to prostatic intraepithelial neoplasia and ultimately to moderately differentiated localized primary tumors, however, c-MYC-driven tumors are unable to progress through the metastatic cascade, suggesting that a "second-hit" is necessary in the milieu of aberrant c-MYC-driven signaling...

Although fluctuations in transcription factor (TF) dosage are often well tolerated, TF dosage modulation can change the target gene expression dynamics and result in significant non-lethal developmental phenotypes. Using MS2/MCP-mediated quantitative live imaging in early Drosophila embryos, we analyzed how changing the gap gene Krüppel (Kr) level affects transcriptional dynamics of the pair-rule gene even-skipped (eve). Halving the Kr dosage leads to a transient posterior expansion of the eve stripe 2 and an anterior shift of stripe 5...

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Krüppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) and ELISA...

The mechanisms underlying glucocorticoid (GC)-induced obesity are poorly understood. Macrophages are the primary targets by which GCs exert pharmacological effects and perform critical functions in adipose tissue homeostasis. Here, we show that macrophages are essential for GC-induced obesity. Dexamethasone (Dex) strongly induced Krüppel-like factor 9 (Klf9) expression in macrophages. Similar to Dex, lentivirus-mediated Klf9 overexpression inhibits M1 and M2a markers expression, causing macrophage deactivation...

UNLABELLED: The cardiovascular system generates and responds to mechanical forces. The heartbeat pumps blood through a network of vascular tubes, which adjust their caliber in response to the hemodynamic environment. However, how endothelial cells in the developing vascular system integrate inputs from circulatory forces into signaling pathways to define vessel caliber is poorly understood. Using vertebrate embryos and in vitro -assembled microvascular networks of human endothelial cells as models, flow and genetic manipulations, and custom software, we reveal that Plexin-D1, an endothelial Semaphorin receptor critical for angiogenic guidance, employs its mechanosensing activity to serve as a crucial positive regulator of the Dorsal Aorta's (DA) caliber...

Patients with the genotype of β0 /β0 for β-thalassemia (β-thal) usually behave as β-thal major (β-TM) phenotype which is transfusion-dependent. The pathophysiology of β-thal is the imbalance between α/β-globin chains. The degree of α/β-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of β-TM. We report a Chinese child who had homozygous β0 -thal and a heterozygous KLF1 mutation...

OBJECTIVE: The function of Kruppel-like factor 3 (KLF3) remains largely unexplored in colorectal cancer (CRC). METHODS: KLF3 expression in CRC was assessed through qPCR, western blotting, immunohistochemical assays, and The Cancer Genome Atlas (TCGA) database. The tumor-promoting capacity of KLF3 was explored by performing in vitro functional experiments using CRC cells. A subcutaneous nude mouse tumor assay was employed to evaluate tumor growth. To further elucidate the interaction between KLF3 and other factors, luciferase reporter assay, agarose gel electrophoresis, and ChIP analysis were performed...