Publications by authors named "Won-Kee Yoon"
Myocardial infarction (MI), a major form of coronary artery disease (CAD), triggers a severe inflammatory response in the heart, resulting in increased cell death and adverse ventricular remodeling. Despite treatment advancements, MI remains a significant risk factor for heart failure, underscoring the necessity for a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7), expressed in various tissues and immune cells, has been implicated in cardiovascular disease, yet its specific role in cardiac immune cells remains poorly understood.
View Article and Find Full Text PDFMitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare.
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- VDUP1 is identified as a tumor suppressor gene, with low expression levels observed in colorectal cancers associated with sporadic cases and ulcerative colitis.
- In a study involving knockout (KO) mice, the absence of VDUP1 was linked to accelerated development of colitis-associated colon cancer (CAC), leading to worse survival and increased tumor burden compared to wild-type (WT) mice.
- The findings suggest that loss of VDUP1 enhances cancer-related cell proliferation and inflammatory responses, indicating the potential for VDUP1-targeting approaches in colon cancer prevention and treatment.
Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.
Biochem Biophys Res Commun
April 2024
Article Synopsis
- PhD finger protein 7 (Phf7) is crucial for spermiogenesis and male fertility, as its absence leads to infertility and growth issues in mice.
- Phf7 knockout mice exhibit lower body weight, reduced bone density, and increased osteoclasts, indicating problems in bone remodeling.
- Lower testosterone levels and reduced expression of key steroidogenesis genes in Phf7 mice suggests that Phf7 deficiency hampers male hormone production, impacting overall bone health.
Article Synopsis
- The study investigates the role of TXNIP (thioredoxin-interacting protein) in the transition of vascular smooth muscle cells (VSMCs) to osteochondrogenic cells, a process that contributes to calcification in atherosclerosis.
- By using mouse models and analyzing single-cell RNA sequencing, the researchers found that TXNIP is downregulated in calcified atherosclerotic lesions, correlating with increased VSMC osteochondrogenic activity.
- Suppressing TXNIP in cultured VSMCs promotes osteodifferentiation and influences pathways related to bone and cartilage formation, suggesting TXNIP plays a significant regulatory role in vascular calcification.
Article Synopsis
- - The study investigates how high levels of lipids in the blood (hyperlipidemia) can trigger inflammation in the aortic valve, which is a key factor in the development of aortic valve disease, although the exact cellular processes involved are still uncertain.
- - Researchers found a connection between low-density lipoprotein (LDL) and increased lipid and macrophage buildup in the aortic valve, using advanced techniques like single-cell RNA sequencing to analyze changes in various cell types during hyperlipidemia.
- - Activation of the PPARγ pathway in valvular endothelial cells appears to play a protective role against inflammation in both mice and human aortic valves, suggesting that promoting this pathway could potentially reduce valvular inflammation related to
N-Myc downstream regulated gene 3 (NDRG3) is a unique pro-tumorigenic member among NDRG family genes, mediating growth signals. Here, we investigated the pathophysiological roles of NDRG3 in relation to cell metabolism by disrupting its functions in liver. Mice with liver-specific KO of NDRG3 (Ndrg3 LKO) exhibited glycogen storage disease (GSD) phenotypes including excessive hepatic glycogen accumulation, hypoglycemia, elevated liver triglyceride content, and several signs of liver injury.
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- - Topoisomerase IIIβ (Top3β) is a unique enzyme in mammals that plays a role in the structure of both DNA and RNA, and its deficiency in mice was studied to understand its link to anxiety and depression-like behaviors.
- - Mice lacking Top3β exhibited reduced anxiety and changes in their circadian rhythms, alongside significant alterations in brain connectivity, particularly between key regions like the olfactory bulb and the cerebellum.
- - The findings suggest that Top3β is crucial for proper brain function and behavior, indicating its potential as a focus for researching neuropsychiatric disorders in humans.
Article Synopsis
- A survey of mouse microbiological contamination was conducted over 6 years, involving 21,292 mice from 206 different facilities in Korea.
- The most commonly detected contaminants were nonpathogenic protozoa (47.2%), with key pathogenic bacteria identified as Staphylococcus aureus, Pasteurella pneumotropica, and Pseudomonas aeruginosa.
- The findings indicate that current contamination levels in mouse facilities primarily involve opportunistic pathogens, and there's a decrease in contamination by more significant pathogens categorized as B or C.
Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in gene utilized by gene trapping.
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- - E2F3 is an important protein that influences cell cycle and growth by interacting with retinoblastoma (RB), a key tumor suppressor.
- - This study focused on the effects of completely removing the E2F3 gene in mice to understand its function.
- - The results showed that while the mice embryos developed without serious issues, they experienced lower body weight, slower growth, bone deformities, and weaker grip, highlighting E2F3's crucial role in muscle and bone development.
Article Synopsis
- * A study on db/db mice (a Type 2 diabetes model) found significant increases in specific lipids (especially ceramides and free fatty acids) in their skin and liver as they developed hyperglycemia.
- * High expressions of certain genes related to lipid synthesis suggest that these lipid changes may play a crucial role in the skin issues observed in diabetes.
Article Synopsis
- Inbred mice, commonly used in biomedical research, face genetic limitations, prompting the study of a new strain (KWM/Hym) from Korean wild mice for better genetic diversity.
- Genetic analysis revealed that KWM/Hym displays significant differences from existing inbred strains, showing a high similarity (96.4%) to the PWK/PhJ strain.
- Morphometric measurements indicated KWM/Hym's unique physical traits, suggesting its potential as a valuable genetic resource for research and addressing the limitations of current lab mice.
Rationale: Monocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during atherosclerosis.
Objective: We sought to examine the transcriptomic profiles of foamy and nonfoamy macrophages isolated from atherosclerotic intima.
Article Synopsis
- A new method was developed to accurately measure pyripyropene A (PPPA), an inhibitor related to cholesterol metabolism, in mouse and human plasma using advanced mass spectrometry techniques.
- * The method effectively separated PPPA from an internal standard, carbamazepine, and demonstrated reliable detection across a wide concentration range.
- * Results showed that the method is suitable for assessing PPPA levels after different administration routes in mice, indicating potential application in human pharmacokinetic studies.
Article Synopsis
- The FRY like transcription coactivator (Fryl) gene, located on chromosome 5, is a less understood paralog of the FRY microtubule binding protein and is conserved across various species, including humans.
- Researchers created a mouse model with a null mutation in the Fryl gene to study its functions, observing that most Fryl mice died shortly after birth, while surviving ones experienced significant growth issues and health complications.
- Histopathological analyses revealed defects primarily in the kidneys of Fryl mice, suggesting that the Fryl gene is crucial for normal kidney development and function, marking the first documentation of Fryl's in vivo roles.
Article Synopsis
- Plasmacytoid dendritic cells (pDCs) are specialized immune cells that produce type I interferon and help promote tolerance in T cells, particularly during inflammation.
- This study discovered that pDCs are present in the aortic intima and that their removal in mice worsened atherosclerosis, indicating their important role in the disease.
- The research demonstrated that pDCs promote the development of regulatory T cells (Tregs) in the aorta, and their absence leads to reduced Treg numbers and IL-10, revealing a protective mechanism against atherosclerosis.
Article Synopsis
- * The peaks of oxidative stress and liver damage occurred at 12 hours after administering 1,3-DCP, with noticeable declines in both indicators afterward.
- * The research indicated that oxidative stress led to cell death in the liver, involving MAPK activation and changes in specific proteins, suggesting a pathway for 1,3-DCP-induced hepatotoxicity.
Article Synopsis
- Hyperlipidemia is linked to atherosclerosis and can be influenced by adipokines like resistin-like molecule alpha (Retnla), whose role in hyperlipidemia is not fully understood.
- Research shows Retnla lowers cholesterol and protects against atherosclerosis in mice without LDL receptors, especially on a high-fat diet.
- Retnla deficiency leads to higher cholesterol and atherosclerosis, while its overexpression improves cholesterol profiles by upregulating a liver enzyme that increases cholesterol excretion, highlighting its potential as a treatment target.
Article Synopsis
- Vitamin D3 up-regulated protein 1 (VDUP1) acts as a growth suppressor, preventing tumor cell growth and the progression of the cell cycle when it's highly expressed.
- Previous research showed that mice lacking VDUP1 (VDUP1 KO) had faster liver regeneration due to better management of cell cycle regulators.
- In this study, VDUP1 KO mice displayed earlier and stronger activation of key proteins involved in liver regeneration (NF-κB, JNK, and STAT-3) following partial liver removal, suggesting that VDUP1 is crucial for starting the liver regeneration process.
Article Synopsis
- Vitamin D(3) upregulated protein 1 (VDUP1) is a crucial tumor suppressor that is significantly reduced in cancers like gastric cancer, and this study investigates its role in Helicobacter pylori-induced gastric tumor development in mice.
- The researchers found that gastric cancer occurred more frequently in VDUP1 knockout mice compared to wild-type mice, which also showed more severe symptoms of gastric inflammation and abnormal cell growth.
- The study suggests that VDUP1 helps regulate gastric cancer by inhibiting certain inflammatory pathways (TNFα, NF-κB, COX-2) that promote cell proliferation, highlighting its potential as a target for cancer therapies.
B cell-activating factor (BAFF) is a key regulator of B lymphocyte development. Signals from BAFF are transmitted through binding to a specific BAFF receptor (BAFF-R). Here, we established screening method to find a specific inhibitor for the interference of BAFF-BAFF-R interactions.
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- - The study investigated the impact of a dietary mixture (red grape extract, soy isoflavone, and L-carnitine, collectively known as RISC) on obesity in mice fed a high-fat diet (HFD), showing that RISC effectively reduced body weight and fat accumulation in a dose-dependent way.
- - RISC treatment also lowered plasma leptin levels and increased high-density lipoprotein (HDL) cholesterol, while not affecting low-density lipoprotein (LDL) cholesterol or triglycerides.
- - The findings suggest that RISC may serve as a beneficial additional treatment for obesity and its related health issues, such as cardiovascular diseases and non-alcoholic fatty liver disease.