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Mfsd2a

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https://www.readbyqxmd.com/read/28827082/mfsd2a-promotes-endothelial-generation-of-inflammation-resolving-lipid-mediators-and-reduces-colitis%C3%A2-in%C3%A2-mice
#1
Federica Ungaro, Carlotta Tacconi, Luca Massimino, Paola Antonia Corsetto, Carmen Correale, Philippe Fonteyne, Andrea Piontini, Valeria Garzarelli, Francesca Calcaterra, Silvia Della Bella, Antonino Spinelli, Michele Carvello, Angela Maria Rizzo, Stefania Vetrano, Luciana Petti, Gionata Fiorino, Federica Furfaro, Domenico Mavilio, Krishna Rao Maddipati, Alberto Malesci, Laurent Peyrin-Biroulet, Silvia D'Alessio, Silvio Danese
BACKGROUND & AIMS: Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation...
August 4, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28823120/deoxynivalenol-and-zearalenone-contaminated-feeds-alter-gene-expression-profiles-in-the-livers-of-piglets
#2
Kondreddy Eswar Reddy, Jin Young Jeong, Yookyung Lee, Hyun-Jeong Lee, Min Seok Kim, Dong-Wook Kim, Hyun Jung Jung, Changyong Choe, Young Kyoon Oh, Sung Dae Lee
Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0...
August 16, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28724654/mfsd2a-major-facilitator-superfamily-domain-containing-2a-attenuates-intracerebral-hemorrhage-induced-blood-brain-barrier-disruption-by-inhibiting-vesicular-transcytosis
#3
Yuan-Rui Yang, Xiao-Yi Xiong, Juan Liu, Li-Rong Wu, Qi Zhong, Kai Zhou, Zhao-You Meng, Liang Liu, Fa-Xiang Wang, Qiu-Wen Gong, Mao-Fan Liao, Chun-Mei Duan, Jie Li, Mei-Hua Yang, Qin Zhang, Chang-Xiong Gong, Qing-Wu Yang
BACKGROUND: Blood-brain barrier (BBB) disruption aggravates brain injury induced by intracerebral hemorrhage (ICH); however, the mechanisms of BBB damage caused by ICH remain elusive. Mfsd2a (major facilitator superfamily domain containing 2a) has been known to play an essential role in BBB formation and function. In this study, we investigated the role and underlying mechanisms of Mfsd2a in BBB permeability regulation after ICH. METHODS AND RESULTS: Using ICH models, we found that Mfsd2a protein expression in perihematomal brain tissues was significantly decreased after ICH...
July 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28674240/molecular-genetic-analysis-of-consanguineous-families-with-primary-microcephaly-identified-pathogenic-variants-in-the-aspm-gene
#4
Muzammil Ahmad Khan, Christian Windpassinger, Muhammad Zeeshan Ali, Muhammad Zubair, Hadia Gul, Safdar Abbas, Saadullah Khan, Muhammad Badar, Ramzi M Mohammad, Zafar Nawaz
Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al. 2014; Alakbarzade et al. 2015;Morris-Rosendahl and Kaindl 2015; Basit et al...
June 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28457600/fatty-acid-transporting-proteins-roles-in-brain-development-aging-and-stroke
#5
REVIEW
Wenting Zhang, Ruiying Chen, Tuo Yang, Na Xu, Jun Chen, Yanqin Gao, R Anne Stetler
Polyunsaturated fatty acids are required for the brain development and significantly impact aging and stroke. Due to the hydrophobicity of fatty acids, fatty acids transportation related proteins that include fatty acid binding proteins (FABPs), long chain acyl-coA synthase (ACS), fatty acid transportation proteins (FATPs), fatty acid translocase (FAT/CD36) and newly reported major facilitator superfamily domain-containing protein (Mfsd2a) play critical roles in the uptake of various fatty acids, especially polyunsaturated fatty acids...
April 21, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28416077/blood-brain-barrier-permeability-is-regulated-by-lipid-transport-dependent-suppression-of-caveolae-mediated-transcytosis
#6
Benjamin J Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A Deik, David D Ginty, Clary B Clish, Chenghua Gu
The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of CNS endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition specifically inhibits the caveolae-mediated transcytotic route readily used in the periphery...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28238797/in%C3%A2-vitro-modeling-of-blood-brain-barrier-with-human-ipsc-derived-endothelial-cells-pericytes-neurons-and-astrocytes-via-notch-signaling
#7
Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K Yamashita
The blood-brain barrier (BBB) is composed of four cell populations, brain endothelial cells (BECs), pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs) into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs) were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A) and efflux transporters (ABCA1, BCRP, PGP, MRP5), and strong barrier function based on tight junctions...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28172768/p004-stimulation-of-cyp450-mediated-%C3%AF-3-docosahexaenoic-acid-metabolism-via-mfsd2a-as-a-novel-therapy-for-inflammatory-bowel-disease
#8
F Ungaro, C Tacconi, C Correale, L Massimino, P Corsetto, A Piontini, P Fonteyne, F Calcaterra, S Della Bella, A Spinelli, M Carvello, A Rizzo, S Vetrano, G Fiorino, F Furfaro, K R Maddipati, S D'Alessio, S Danese
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/27885588/a-mouse-model-reveals-that-mfsd2a-is-critical-for-unfolded-protein-response-upon-exposure-to-tunicamycin
#9
Hiroshi Moritake, Megumi Obara, Yusuke Saito, Ayako Kashimada, Masatoshi Takagi, Megumi Funakoshi-Tago, Tomofusa Fukuyama, Mikio Yoshioka, Akira Inoue, Hiroyuki Komatsu, Hideki Nishitoh, Hiroaki Kataoka, Hiroyuki Nunoi
Major facilitator superfamily domain containing 2a (Mfsd2a) is a member of the major facilitator superfamily. Mfsd2a functions as a transporter for docosahexaenoic acid and also plays a role in the unfolded protein response (UPR) upon tunicamycin (TM) exposure. UPR is involved in the pathogenesis of various human diseases. TM and thapsigargin are representative experimental reagents that induce UPR. To elucidate the detailed function of Mfsd2a in UPR in vivo, we generated Mfsd2a-deficient mice and investigated the role of Mfsd2a during UPR induced by TM or thapsigargin...
April 2017: Human Cell
https://www.readbyqxmd.com/read/27864326/both-maternal-and-offspring-elovl2-genotypes-determine-systemic-dha-levels-in-perinatal-mice
#10
Anna M Pauter, Sofia Trattner, Amanda Gonzalez-Bengtsson, Emanuela Talamonti, Abolfazl Asadi, Olga Dethlefsen, Anders Jacobsson
The molecular details relevant to dietary supplementation of the omega-3 fatty acid DHA in mothers as well as in their offspring are not clear. The PUFA elongase, elongation of very long-chain fatty acid (ELOVL)2, is a critical enzyme in the formation of DHA in mammals. In order to address the question regarding the origin of DHA during perinatal life, we have used DHA-deficient Elovl2-ablated mice as a model system to analyze the maternal impact on the DHA level in their offspring of various genotypes. Elovl2(-/-) mothers maintained on control diet had significantly lower systemic levels of DHA compared with the Elovl2(+/-) and Elovl2(+/+) mothers...
January 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27857132/mfsd2a-hepatocytes-repopulate-the-liver-during-injury-and-regeneration
#11
Wenjuan Pu, Hui Zhang, Xiuzhen Huang, Xueying Tian, Lingjuan He, Yue Wang, Libo Zhang, Qiaozhen Liu, Yan Li, Yi Li, Huan Zhao, Kuo Liu, Jie Lu, Yingqun Zhou, Pengyu Huang, Yu Nie, Yan Yan, Lijian Hui, Kathy O Lui, Bin Zhou
Hepatocytes are functionally heterogeneous and are divided into two distinct populations based on their metabolic zonation: the periportal and pericentral hepatocytes. During liver injury and regeneration, the cellular dynamics of these two distinct populations remain largely elusive. Here we show that major facilitator super family domain containing 2a (Mfsd2a), previously known to maintain blood-brain barrier function, is a periportal zonation marker. By genetic lineage tracing of Mfsd2a(+) periportal hepatocytes, we show that Mfsd2a(+) population decreases during liver homeostasis...
November 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27008858/mfsd2a-is-a-transporter-for-the-essential-%C3%AF-3-fatty-acid-docosahexaenoic-acid-dha-in-eye-and-is-important-for-photoreceptor-cell-development
#12
Bernice H Wong, Jia Pei Chan, Amaury Cazenave-Gassiot, Rebecca W Poh, Juat Chin Foo, Dwight L A Galam, Sujoy Ghosh, Long N Nguyen, Veluchamy A Barathi, Sia W Yeo, Chi D Luu, Markus R Wenk, David L Silver
Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth...
May 13, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26945070/structural-insights-into-the-transport-mechanism-of-the-human-sodium-dependent-lysophosphatidylcholine-transporter-mfsd2a
#13
Debra Q Y Quek, Long N Nguyen, Hao Fan, David L Silver
Major facilitator superfamily domain containing 2A (MFSD2A) was recently characterized as a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier endothelium. It is the primary route for importation of docosohexaenoic acid and other long-chain fatty acids into fetal and adult brain and is essential for mouse and human brain growth and function. Remarkably, MFSD2A is the first identified major facilitator superfamily member that uniquely transports lipids, implying that MFSD2A harbors unique structural features and transport mechanism...
April 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26869380/placental-mfsd2a-transporter-is-related-to-decreased-dha-in-cord-blood-of-women-with-treated-gestational-diabetes
#14
María T Prieto-Sánchez, María Ruiz-Palacios, José E Blanco-Carnero, Ana Pagan, Christian Hellmuth, Olaf Uhl, Wolfgang Peissner, Antonio J Ruiz-Alcaraz, Juan J Parrilla, Berthold Koletzko, Elvira Larqué
BACKGROUND & AIMS: Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers...
April 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/26853155/effects-of-individually-silenced-n-glycosylation-sites-and-non-synonymous-single-nucleotide-polymorphisms-on-the-fusogenic-function-of-human-syncytin-2
#15
Lina Cui, Huiying Wang, Xiaoyin Lu, Rui Wang, Ru Zheng, Yue Li, Xiaokui Yang, Wen-Tong Jia, Yangyu Zhao, Yongqing Wang, Haibin Wang, Yan-Ling Wang, Cheng Zhu, Hai-Yan Lin, Hongmei Wang
The placental syncytiotrophoblast, which is formed by the fusion of cytotrophoblast cells, is indispensable for the establishment and maintenance of normal pregnancy. The human endogenous retrovirus envelope glycoprotein syncytin-2 is the most important player in mediating trophoblast cell-cell fusion as a fusogen. We constructed expression plasmids of wild-type and 21 single-amino-acid substitution mutants of syncytin-2, including 10 N-glycosylation sites individually silenced by mutagenizing N to Q, 1 naturally occurring single-nucleotide polymorphism (SNP) N118S that introduced an N-glycosylation site, and another 10 non-synonymous SNPs located within important functional domains...
March 3, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/26747400/mfsd2a-based-pharmacological-strategies-for-drug-delivery-across-the-blood-brain-barrier
#16
Jing-Zhang Wang, Ning Xiao, Ying-Zhou Zhang, Chao-Xian Zhao, Xin-Hua Guo, Li-Min Lu
The blood-brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some substances across the BBB. Mfsd2a is the first inhibitor of the transcytosis and the first transporter for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA) in BMECs. The crucial dual function of Mfsd2a puts forward two kinds of Mfsd2a-based strategies for carrying drugs from blood to the CNS...
February 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26648110/identification-of-genes-associated-with-smad3-dependent-renal-injury-by-rna-seq-based-transcriptome-analysis
#17
Qin Zhou, Yuanyan Xiong, Xiao R Huang, Patrick Tang, Xueqing Yu, Hui Y Lan
Transforming growth factor-β/Smad3 signaling plays a critical role in the process of chronic kidney disease (CKD), but targeting Smad3 systematically may cause autoimmune disease by impairing immunity. In this study, we used whole-transcriptome RNA-sequencing to identify the differential gene expression profile, gene ontology, pathways, and alternative splicing related to TGF-β/Smad3 in CKD. To explore common dysregulation of genes associated with Smad3-dependent renal injury, kidney tissues of Smad3 wild-type and knockout mice with immune (anti-glomerular basement membrane glomerulonephritis) and non-immune (obstructive nephropathy)-mediated CKD were used for RNA-sequencing analysis...
December 9, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26111510/lipid-transport-and-human-brain-development
#18
Christer Betsholtz
How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.
July 2015: Nature Genetics
https://www.readbyqxmd.com/read/26005868/inactivating-mutations-in-mfsd2a-required-for-omega-3-fatty-acid-transport-in-brain-cause-a-lethal-microcephaly-syndrome
#19
Alicia Guemez-Gamboa, Long N Nguyen, Hongbo Yang, Maha S Zaki, Majdi Kara, Tawfeg Ben-Omran, Naiara Akizu, Rasim Ozgur Rosti, Basak Rosti, Eric Scott, Jana Schroth, Brett Copeland, Keith K Vaux, Amaury Cazenave-Gassiot, Debra Q Y Quek, Bernice H Wong, Bryan C Tan, Markus R Wenk, Murat Gunel, Stacey Gabriel, Neil C Chi, David L Silver, Joseph G Gleeson
Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and, although it is considered essential, deficiency has not been linked to disease. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the major facilitator superfamily domain-containing 2a (MFSD2A) protein. MFSD2A transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues...
July 2015: Nature Genetics
https://www.readbyqxmd.com/read/26005865/a-partially-inactivating-mutation-in-the-sodium-dependent-lysophosphatidylcholine-transporter-mfsd2a-causes-a-non-lethal-microcephaly-syndrome
#20
Vafa Alakbarzade, Abdul Hameed, Debra Q Y Quek, Barry A Chioza, Emma L Baple, Amaury Cazenave-Gassiot, Long N Nguyen, Markus R Wenk, Arshia Q Ahmad, Ajith Sreekantan-Nair, Michael N Weedon, Phil Rich, Michael A Patton, Thomas T Warner, David L Silver, Andrew H Crosby
The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity...
July 2015: Nature Genetics
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