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https://www.readbyqxmd.com/read/28827473/restoration-of-circulating-mfge8-milk-fat-globule-egf-factor-8-attenuates-cardiac-hypertrophy-through-inhibition-of-akt-pathway
#1
Ke-Qiong Deng, Jing Li, Zhi-Gang She, Jun Gong, Wen-Lin Cheng, Fu-Han Gong, Xue-Yong Zhu, Yan Zhang, Zhihua Wang, Hongliang Li
Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients...
August 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28698173/interferon-regulatory-factor-5-controls-necrotic-core-formation-in-atherosclerotic-lesions-by-impairing-efferocytosis
#2
Anusha N Seneviratne, Andreas Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq Khoyratty, David Saliba, Michael E Goddard, Stephen N Sansom, Isabel Goncalves, Rob Krams, Irina A Udalova, Claudia Monaco
BACKGROUND: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. METHODS: We investigated the role of IRF5 in atherosclerosis in 2 complementary models...
September 19, 2017: Circulation
https://www.readbyqxmd.com/read/28600866/bone-mass-is-compromised-by-the-chemotherapeutic-trabectedin-in-association-with-effects-on-osteoblasts-and-macrophage-efferocytosis
#3
Benjamin P Sinder, Laura Zweifler, Amy J Koh, Megan N Michalski, Lorenz C Hofbauer, Jose Ignacio Aguirre, Hernan Roca, Laurie K McCauley
Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in bone homeostasis is not well understood. Interestingly, apoptosis is a pivotal feature of cellular regulation and the primary fate of osteoblasts is apoptosis. Efferocytosis (phagocytosis of apoptotic cells) is a key physiologic process for the homeostasis of many tissues, and is associated with expression of osteoinductive factors. To test effects of macrophage depletion and compromised phagocytosis on bone, 16 wk old male C57BL/6J mice were treated with trabectedin - a chemotherapeutic with established anti-macrophage effects...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28375666/glucocorticoid-receptor-chip-seq-identifies-plcd1-as-a-klf15-target-that-represses-airway-smooth-muscle-hypertrophy
#4
Sarah K Sasse, Vineela Kadiyala, Thomas Danhorn, Reynold A Panettieri, Tzu L Phang, Anthony N Gerber
Glucocorticoids exert important therapeutic effects on airway smooth muscle (ASM), yet few direct targets of glucocorticoid signaling in ASM have been definitively identified. Here, we show that the transcription factor, Krüppel-like factor 15 (KLF15), is directly induced by glucocorticoids in primary human ASM, and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA polymerase (RNAP) II and glucocorticoid receptor (GR) occupancy to identify phospholipase C delta 1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy...
August 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28320530/single-cell-rna-sequence-analysis-of-mouse-glomerular-mesangial-cells-uncovers-mesangial-cell-essential-genes
#5
Yuqiu Lu, Yuting Ye, Qianqian Yang, Shaolin Shi
Mesangial cells are essential for the structure and function of glomeruli, but the mechanisms underlying these roles are not well understood. Here, we performed a single-cell RNA-sequence (RNA-seq) analysis of mouse mesangial cells using the Fluidigm C1 platform. We found that gene expression in individual mesangial cells was tremendously heterogeneous, with mean correlation coefficients of 0.20, and most mesangial genes were actually expressed in only a portion of mesangial cells and are therefore presumably dispensable...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28115038/identification-of-mfge8-in-mesenchymal-stem-cell-secretome-as-an-anti-fibrotic-factor-in-liver-fibrosis
#6
Yu Jin Jang, Su Yeon An, Jong-Hoon Kim
The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the TGFβ/Smad-signaling...
February 2017: BMB Reports
https://www.readbyqxmd.com/read/27956229/milk-fat-globule-egf-factor-8-secreted-by-mesenchymal-stem-cells-protects-against-liver-fibrosis-in-mice
#7
Su Yeon An, Yu Jin Jang, Hee-Joung Lim, Jiyou Han, Jaehun Lee, Gyunggyu Lee, Ji Young Park, Seo-Young Park, Ji Hyang Kim, Byung-Rok Do, Choongseong Han, Hee-Kyung Park, Ok-Hee Kim, Myeong Jun Song, Say-June Kim, Jong-Hoon Kim
BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadrupole time-of-flight mass spectrometry...
April 2017: Gastroenterology
https://www.readbyqxmd.com/read/27812539/mfge8-regulates-enterocyte-lipid-storage-by-promoting-enterocyte-triglyceride-hydrolase-activity
#8
Amin Khalifeh-Soltani, Deepti Gupta, Arnold Ha, Jahangir Iqbal, Mahmood Hussain, Michael J Podolsky, Kamran Atabai
The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27092791/%C3%AE-8%C3%AE-1-integrin-regulates-nutrient-absorption-through-an-mfge8-pten-dependent-mechanism
#9
Amin Khalifeh-Soltani, Arnold Ha, Michael J Podolsky, Donald A McCarthy, William McKleroy, Saeedeh Azary, Stephen Sakuma, Kevin M Tharp, Nanyan Wu, Yasuyuki Yokosaki, Daniel Hart, Andreas Stahl, Kamran Atabai
Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity...
April 19, 2016: ELife
https://www.readbyqxmd.com/read/27050058/coagulation-gene-expression-profiling-in-infants-with-necrotizing-enterocolitis
#10
Stefano Giuliani, Yew-Wei Tan, Dongling Zheng, Evmorfia Petropoulou, Ali Sohail, Sarah Bradley, Justin Richards, Nigel Kennea, Yalda Jamshidi
OBJECTIVES: Coagulopathy and mesenteric thrombosis are common in premature neonates with necrotizing enterocolitis (NEC). This pilot study aimed to investigate the hypothesis that there are changes in the gene expression related to the coagulation and anticoagulation systems in NEC. METHODS: Consecutive neonates (n = 11) with NEC (Bell stages 2-3) were recruited. Two comparison groups, matched for birth weight and corrected gestational age, were selected based on the absence of inflammation and coagulopathy (healthy control, n = 10), or the presence of a confirmed blood infection (sepsis control, n = 12)...
December 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/26819373/myeloid-epithelial-reproductive-receptor-tyrosine-kinase-and-milk-fat-globule-epidermal-growth-factor-8-coordinately-improve-remodeling-after-myocardial-infarction-via-local-delivery-of-vascular-endothelial-growth-factor
#11
Kiave-Yune Howangyin, Ivana Zlatanova, Cristina Pinto, Anta Ngkelo, Clément Cochain, Marie Rouanet, José Vilar, Mathilde Lemitre, Christian Stockmann, Bernd K Fleischmann, Ziad Mallat, Jean-Sébastien Silvestre
BACKGROUND: In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction. METHODS AND RESULTS: We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature...
March 1, 2016: Circulation
https://www.readbyqxmd.com/read/26376757/milk-fat-globule-epidermal-growth-factor-factor-viii-downregulates-interleukin-17-expression-in-sepsis-by%C3%A2-modulating-stat3-activation
#12
Cindy Cen, Monowar Aziz, Weng-Lang Yang, Jeffrey Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in inflammation. In sepsis, interleukin (IL)-17 acts as a proinflammatory cytokine to exaggerate systemic inflammation. We hypothesize that MFG-E8 downregulates IL-17 expression in sepsis. METHODS: Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) at a dosage of 20 μg/kg body weight or phosphate-buffered saline was concurrently injected...
February 2016: Surgery
https://www.readbyqxmd.com/read/26240339/astrocytes-phagocytose-focal-dystrophies-from-shortening-myelin-segments-in-the-optic-nerve-of-xenopus-laevis-at-metamorphosis
#13
Elizabeth A Mills, Chung-ha O Davis, Eric A Bushong, Daniela Boassa, Keun-Young Kim, Mark H Ellisman, Nicholas Marsh-Armstrong
Oligodendrocytes can adapt to increases in axon diameter through the addition of membrane wraps to myelin segments. Here, we report that myelin segments can also decrease their length in response to optic nerve (ON) shortening during Xenopus laevis metamorphic remodeling. EM-based analyses revealed that myelin segment shortening is accomplished by focal myelin-axon detachments and protrusions from otherwise intact myelin segments. Astrocyte processes remove these focal myelin dystrophies using known phagocytic machinery, including the opsonin milk fat globule-EGF factor 8 (Mfge8) and the downstream effector ras-related C3 botulinum toxin substrate 1 (Rac1)...
August 18, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26227178/recurrent-fusion-transcripts-detected-by-whole-transcriptome-sequencing-of-120-primary-breast-cancer-samples
#14
Jisun Kim, Sehwan Kim, Seyoon Ko, Yong-ho In, Hyeong-Gon Moon, Soo Kyung Ahn, Min Kyoon Kim, Minju Lee, Jin-Ha Hwang, Young Seok Ju, Jong-Il Kim, Dong-Young Noh, Sun Kim, Jung-Hoon Park, Hwanseok Rhee, Sunghoon Kim, Wonshik Han
Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall...
November 2015: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/26049031/quantitative-proteomics-provides-new-insights-into-chicken-eggshell-matrix-protein-functions-during-the-primary-events-of-mineralisation-and-the-active-calcification-phase
#15
Pauline Marie, Valérie Labas, Aurélien Brionne, Grégoire Harichaux, Christelle Hennequet-Antier, Alejandro B Rodriguez-Navarro, Yves Nys, Joël Gautron
Eggshell is a bioceramic composed of 95% calcium carbonate mineral and 3.5% organic matrix. Its structural organisation is controlled by its organic matrix. We have used quantitative proteomics to study four key stages of shell mineralisation: 1) widespread deposition of amorphous calcium carbonate (ACC), 2) ACC transformation into crystalline calcite aggregates, 3) formation of larger calcite crystal units and 4) development of a columnar structure with preferential calcite crystal orientation. This approach explored the distribution of 216 shell matrix proteins found at the four stages...
August 3, 2015: Journal of Proteomics
https://www.readbyqxmd.com/read/25936875/mfge8-integrin-%C3%AE-3-pathway-alleviates-apoptosis-and-inflammation-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats
#16
Fei Liu, Yujie Chen, Qin Hu, Bo Li, Junjia Tang, Yue He, Zongduo Guo, Hua Feng, Jiping Tang, John H Zhang
BACKGROUND: Milk fat globule-epidermal growth factor-factor 8(MFGE8)/Integrin β3 pathway was reported to be involved in reducing oxidative stress and early brain injury after subarachnoid hemorrhage (SAH). In the present study, the potential effects of MFGE8 and its receptor Integrin β3 in the inhibition of apoptosis and neuroinflammation in early brain injury after SAH were investigated. METHODS: Ninety-five (95) male Sprague-Dawley rats were used. The SAH model was induced by endovascular perforation...
October 2015: Experimental Neurology
https://www.readbyqxmd.com/read/25867181/milk-fat-globule-egf-factor-viii-attenuates-cns-injury-by-promoting-neural-stem-cell-proliferation-and-migration-after-cerebral-ischemia
#17
Cletus Cheyuo, Monowar Aziz, Weng-Lang Yang, Asha Jacob, Mian Zhou, Ping Wang
The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFG-E8), a secreted glycoprotein serves several cellular functions by binding to its receptor, αv β3-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8-/-) mice by transient middle cerebral artery occlusion (tMCAO)...
2015: PloS One
https://www.readbyqxmd.com/read/25342030/recombinant-milk-fat-globule-egf-factor-8-reduces-oxidative-stress-via-integrin-%C3%AE-3-nuclear-factor-erythroid-2-related-factor-2-heme-oxygenase-pathway-in-subarachnoid-hemorrhage-rats
#18
Fei Liu, Qin Hu, Bo Li, Anatol Manaenko, Yujie Chen, Junjia Tang, Zongduo Guo, Jiping Tang, John H Zhang
BACKGROUND AND PURPOSE: Milk fat globule-EGF factor-8 (MFGE8) has been reported to be neuroprotective in ischemic stroke. However, the effects of MFGE8 in early brain injury after subarachnoid hemorrhage (SAH) have not been investigated. We investigated the role of MFGE8 in early brain injury and the potential mechanisms in antioxidation after SAH. METHODS: Two dosages (1 μg and 3.3 μg) of recombinant human MFGE8 were injected intracerebroventricularly at 1.5 hours after SAH...
December 2014: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/25284052/quantitative-proteomics-and-bioinformatic-analysis-provide-new-insight-into-protein-function-during-avian-eggshell-biomineralization
#19
Pauline Marie, Valérie Labas, Aurélien Brionne, Grégoire Harichaux, Christelle Hennequet-Antier, Yves Nys, Joël Gautron
UNLABELLED: Gallus gallus eggshell is a bioceramic composed of 95% calcium carbonate in calcitic form and 3.5% extracellular organic matrix. The calcification process occurs in the uterine fluid where biomineralization follows a temporal sequence corresponding to the initiation, growth and termination stages of crystal growth. Eggshell texture and its ultrastructure are regulated by organic matrix proteins, which control mineralization process and influence the eggshell biomechanical properties...
January 15, 2015: Journal of Proteomics
https://www.readbyqxmd.com/read/25206960/different-immunogenicity-but-similar-antitumor-efficacy-of-two-dna-vaccines-coding-for-an-antigen-secreted-in-different-membrane-vesicle-associated-forms
#20
Christine Sedlik, James Vigneron, Lea Torrieri-Dramard, Fabien Pitoiset, Jordan Denizeau, Caroline Chesneau, Philippe de la Rochere, Olivier Lantz, Clotilde Thery, Bertrand Bellier
The induction of an active immune response to control or eliminate tumours is still an unfulfilled challenge. We focused on plasmid DNA vaccines using an innovative approach whereby the antigen is expressed in association with extracellular vesicles (EVs) to facilitate antigen cross-presentation and improve induced immunity. Our two groups had independently shown previously that DNA vaccines encoding EV-associated antigens are more efficient at inducing cytotoxic T-cell responses than vaccines encoding the non-EV-associated antigen...
2014: Journal of Extracellular Vesicles
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