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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...
2016: ELife
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's 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)...
March 31, 2016: Journal of Pediatric Gastroenterology and Nutrition
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
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
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
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
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
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
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
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
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
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
Björn Spittau, Jennifer Rilka, Elsa Steinfath, Tanja Zöller, Kerstin Krieglstein
Milk fat globule-epidermal growth factor-factor 8 (Mfge8) has been described as an essential molecule during microglia-mediated clearance of apoptotic cells via binding to phosphatidylserine residues and subsequent phagocytosis. Impaired uptake of apoptotic cells by microglia results in prolonged inflammatory responses and damage of healthy cells. Although the mechanisms of Mfge8-mediated engulfment of apoptotic cells are well understood, endogenous or exogenous factors that regulate Mfge8 expression remain elusive...
January 2015: Glia
Takafumi Jinushi, Yoshihiko Shibayama, Ichiro Kinoshita, Satoshi Oizumi, Masahisa Jinushi, Tadahiro Aota, Toshiyuki Takahashi, Shoichi Horita, Hirotoshi Dosaka-Akita, Ken Iseki
A component of polycomb repressor complex 2, enhancer of zeste homolog 2 (EZH2), plays an important role in tumor malignancy and metastasis, while milk fat globule-epidermal growth factor-factor 8 (MFGE8) plays a key role in tumor progression and prognosis. MicroRNAs (miRs) are also critically involved in various physiological and pathological processes. We here evaluated the relationship between overall survival (OS) in colorectal cancer patients and the expression of onco-miRs and miRs, which may target EZH2 and MFGE8...
December 2014: Cancer Medicine
Toshiharu Abe, Jieun Shin, Kavita Hosur, Mark C Udey, Triantafyllos Chavakis, George Hajishengallis
The glycoprotein milk fat globule-epidermal growth factor factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether it plays a role in bone homeostasis has not been established. In this study, we show for the first time, to our knowledge, that osteoclasts express and are regulated by MFG-E8. Bone marrow-derived osteoclast precursors from MFG-E8-deficient (Mfge8(-/-)) mice underwent increased receptor activator of NF-κB ligand-induced osteoclastogenesis, leading to enhanced resorption pit formation compared with wild-type controls...
August 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
L Fontanesi, D G Calò, G Galimberti, R Negrini, R Marino, A Nardone, P Ajmone-Marsan, V Russo
We genotyped 58 single nucleotide polymorphisms (SNPs) in 25 candidate genes in about 800 Italian Holstein sires. Fifty-six (minor allele frequency >0.02) were used to evaluate their association with single traits: milk yield (MY), milk fat yield (FY), milk protein yield (PY), milk fat percentage (FP), milk protein percentage (PP), milk somatic cell count (MSCC); and complex indexes: longevity, fertility and productivity-functionality type (PFT), using deregressed proofs, after adjustment for familial relatedness...
August 2014: Animal Genetics
Amin Khalifeh-Soltani, William McKleroy, Stephen Sakuma, Yuk Yin Cheung, Kevin Tharp, Yifu Qiu, Scott M Turner, Ajay Chawla, Andreas Stahl, Kamran Atabai
Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance...
February 2014: Nature Medicine
Adriano Aguzzi, Jan Kranich, Nike Julia Krautler
Follicular dendritic cells (FDCs) were originally identified by their specific morphology and by their ability to trap immune-complexed antigen in B cell follicles. By virtue of the latter as well as the provision of chemokines, adhesion molecules, and trophic factors, FDCs participate in the shaping of B cell responses. Importantly, FDCs also supply tingible body macrophages (TBMs) with the eat-me-signaling molecule milk fat globule-EGF factor 8 (Mfge8), thereby enabling the disposal of apoptotic B cells. Recent studies have provided fundamental insights into the multiple functions of FDCs in both physiological and pathophysiological contexts and into their origin...
March 2014: Trends in Immunology
Angélique Bobrie, Marina Colombo, Sophie Krumeich, Graça Raposo, Clotilde Théry
Exosomes are extracellular vesicles of 50 to 100 nm in diameter, released by many cell types. Exosomes are formed inside the cell in intracellular endosomal compartments and are secreted upon fusion of these compartments with the plasma membrane. Cells also secrete other types of membrane vesicles, for instance, by outward budding from the plasma membrane, and although some of them clearly differ from exosomes by their structural features (larger size), others are possibly more difficult to separate. Here, using Rab27a inhibition to modulate exosome secretion, we show the existence of at least 2 distinct populations of vesicles after purification by classical ultracentrifugation from mouse tumor cell conditioned medium...
2012: Journal of Extracellular Vesicles
Lorenzo Tibaldi, Shirley Leyman, André Nicolas, Sofie Notebaert, Melissa Dewulf, Thu Hoa Ngo, Claudia Zuany-Amorim, Nathalie Amzallag, Isabelle Bernard-Pierrot, Xavier Sastre-Garau, Clotilde Théry
Milk Fat Globule--EGF--factor VIII (MFGE8), also called lactadherin, is a secreted protein, which binds extracellularly to phosphatidylserine and to αvβ3 and αvβ5 integrins. On human and mouse cells expressing these integrins, such as endothelial cells, phagocytes and some tumors, MFGE8/lactadherin has been shown to promote survival, epithelial to mesenchymal transition and phagocytosis. A protumoral function of MFGE8 has consequently been documented for a few types of human cancers, including melanoma, a subtype of breast cancers, and bladder carcinoma...
2013: PloS One
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