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Kaede Takahashi, Kaori Fukushima, Yuka Onishi, Karin Inui, Yusuke Node, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells...
January 29, 2017: Biochemical and Biophysical Research Communications
Christeen Ramane J Pedurupillay, Erlend Christoffer Sommer Landsend, Magnus Dehli Vigeland, Muhammad Ansar, Eirik Frengen, Doriana Misceo, Petter Strømme
We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision...
July 27, 2016: Genes
Cong Li, Wentao Cai, Chenghao Zhou, Hongwei Yin, Ziqi Zhang, Juan J Loor, Dongxiao Sun, Qin Zhang, Jianfeng Liu, Shengli Zhang
Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non-lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration...
2016: Scientific Reports
Biljana Stangeland, Awais A Mughal, Zanina Grieg, Cecilie Jonsgar Sandberg, Mrinal Joel, Ståle Nygård, Torstein Meling, Wayne Murrell, Einar O Vik Mo, Iver A Langmoen
Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures...
September 22, 2015: Oncotarget
Abid Jan, Sulman Basit, Salma M Wakil, Khushnooda Ramzan, Wasim Ahmad
Autosomal recessive forms of hair loss (alopecia) disorders have previously been associated with variants in at least five different genes including hairless (HR), desmoglein-4 (DSG4), desmocollin-3 (DSC3), lipase-H (LIPH), and lysophosphatidic acid receptor 6 (LPAR6). Here, we report the first familial case of alopecia resulting from a novel homozygous variant in the DSP gene. Since previous reports indicated the presence of heart abnormalities in patients carrying variants in the DSP gene; therefore, the echocardiographic evaluations of all affected members were performed...
November 2015: Archives of Dermatological Research
Ke Xu, Lu Ma, Yang Li, Fang Wang, Gu-Yan Zheng, Zhijun Sun, Feng Jiang, Yundai Chen, Huirong Liu, Aimin Dang, Xi Chen, Jerold Chun, Xiao-Li Tian
Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total...
September 2015: Hypertension
Ryota Hayashi, Asuka Inoue, Yasushi Suga, Junken Aoki, Yutaka Shimomura
BACKGROUND: Woolly hair (WH) is a hair shaft anomaly characterized by tightly-curled hair and is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal dominant or recessive inheritance. The autosomal recessive form of WH (ARWH) is caused by mutations in either lipase H (LIPH) or lysophosphatidic acid receptor 6 (LPAR6) gene, encoding an LPA-producing enzyme PA-PLA1α and an LPA receptor LPA6, respectively. OBJECTIVE: To define the molecular basis of ARWH/hypotrichosis in a Japanese family...
June 2015: Journal of Dermatological Science
Wanda K O'Neal, Paul Gallins, Rhonda G Pace, Hong Dang, Whitney E Wolf, Lisa C Jones, XueLiang Guo, Yi-Hui Zhou, Vered Madar, Jinyan Huang, Liming Liang, Miriam F Moffatt, Garry R Cutting, Mitchell L Drumm, Johanna M Rommens, Lisa J Strug, Wei Sun, Jaclyn R Stonebraker, Fred A Wright, Michael R Knowles
Variation in cystic fibrosis (CF) phenotypes, including lung disease severity, age of onset of persistent Pseudomonas aeruginosa (P. aeruginosa) lung infection, and presence of meconium ileus (MI), has been partially explained by genome-wide association studies (GWASs). It is not expected that GWASs alone are sufficiently powered to uncover all heritable traits associated with CF phenotypic diversity. Therefore, we utilized gene expression association from lymphoblastoid cells lines from 754 p.Phe508del CF-affected homozygous individuals to identify genes and pathways...
February 5, 2015: American Journal of Human Genetics
Antonio Mazzocca, Francesco Dituri, Flavia De Santis, Addolorata Filannino, Chiara Lopane, Regina C Betz, Ying-Yi Li, Naofumi Mukaida, Peter Winter, Cosimo Tortorella, Gianluigi Giannelli, Carlo Sabbà
The aberrant processes driving hepatocellular carcinoma (HCC) are not fully understood. Lysophosphatidic acid receptors (LPAR) are commonly overexpressed in HCC, but their contributions to malignant development are not well established. In this report, we show that aberrant expression of LPAR6 sustains tumorigenesis and growth of HCC. Overexpression of LPAR6 in HCC specimens associated with poor survival in a cohort of 128 patients with HCC. We took a genetic approach to elucidate how LPAR6 sustains the HCC tumorigenic process, including through an expression profiling analysis to identify genes under the control of LPAR6...
February 1, 2015: Cancer Research
A Ketscher, C A Jilg, D Willmann, B Hummel, A Imhof, V Rüsseler, S Hölz, E Metzger, J M Müller, R Schüle
Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN)...
2014: Oncogenesis
Ryota Hayashi, Shigeki Inui, Muhammad Farooq, Masaaki Ito, Yutaka Shimomura
Autosomal recessive woolly hair (ARWH) is characterized by short and tightly curled scalp hair without any obvious complications. The disease is known to be caused by either lipase H (LIPH) or LPAR6 genes. Proteins encoded by these two genes are closely related to each other in a lipid-signaling pathway that is believed to play crucial roles in hair follicle development and hair growth. In the Japanese population, most affected individuals with ARWH have been shown to carry two prevalent founder mutations in the LIPH gene, c...
October 2014: Journal of Dermatology
Yuji Morimoto, Shoichi Ishii, Jun-Ichi Ishibashi, Kazutaka Katoh, Toshifumi Tsujiuchi, Nao Kagawa, Nobuyuki Fukushima
Lysophosphatidic acid (LPA) signaling is known to play biological and pathophysiological roles in many types of animals. Medaka (Oryzias latipes) is an experimental fish that can be easily maintained, propagated, and analyzed, and whose genome has been completely sequenced. However, there is limited information available regarding medaka LPA receptors. Here, using information from the medaka genome database, we examine the genomic structures, expression, and functions of six LPA receptor genes, Lpar1-Lpar6...
November 10, 2014: Gene
Syed Irfan Raza, Dost Muhammad, Abid Jan, Raja Hussain Ali, Mubashir Hassan, Wasim Ahmad, Sajid Rashid
Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p...
2014: PloS One
D Brünnert, M Sztachelska, F Bornkessel, N Treder, S Wolczynski, P Goyal, M Zygmunt
In the luteal phase, human endometrial stromal cells (HESCs) undergo proliferation, migration and differentiation during the decidualization process under the control of the ovarian steroids progesterone and estrogen. Proper decidualization of stromal cells is required for blastocyst implantation and the development of pregnancy. The proliferation, migration and differentiation of HESCs in decidualization do not require the presence of a blastocyst but are greatly accelerated during implantation. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are potent bioactive lysophospholipids that have critical roles in various physiological and pathophysiological processes, including inflammation, angiogenesis and cancer...
October 2014: Molecular Human Reproduction
R C Betz
The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous disorders with decreased or absent hair. Clinical classification of the isolated alopecias is based upon the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Therapy does not exist for these rare forms of alopecia. However, molecular genetic diagnosis is possible for the identification of the genetic causes and for the specification of the recurrence risk...
June 2014: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Alexander R Pinto, James W Godwin, Anjana Chandran, Lucy Hersey, Alexei Ilinykh, Ryan Debuque, Lina Wang, Nadia A Rosenthal
Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age...
May 2014: Aging
Kerri A Simo, David J Niemeyer, Erin M Hanna, Jacob H Swet, Kyle J Thompson, David Sindram, David A Iannitti, Ashley L Eheim, Eugene Sokolov, Valentina Zuckerman, Iain H McKillop
BACKGROUND: Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1-6 expression in regenerating liver following two-thirds partial hepatectomy (PHx). METHODS: Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined...
June 2014: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Yasuyuki Kihara, Michael Maceyka, Sarah Spiegel, Jerold Chun
Lysophospholipids encompass a diverse range of small, membrane-derived phospholipids that act as extracellular signals. The signalling properties are mediated by 7-transmembrane GPCRs, constituent members of which have continued to be identified after their initial discovery in the mid-1990s. Here we briefly review this class of receptors, with a particular emphasis on their protein and gene nomenclatures that reflect their cognate ligands. There are six lysophospholipid receptors that interact with lysophosphatidic acid (LPA): protein names LPA1 - LPA6 and italicized gene names LPAR1-LPAR6 (human) and Lpar1-Lpar6 (non-human)...
August 2014: British Journal of Pharmacology
Timothy J Geach, Laura Faas, Christelle Devader, Anai Gonzalez-Cordero, Jacqueline M Tabler, Hannah Brunsdon, Harry V Isaacs, Leslie Dale
Lysophosphatidic acid (LPA) has wide-ranging effects on many different cell types, acting through G-protein-coupled receptors such as LPAR6. We show that Xenopus lpar6 is expressed from late blastulae and is enriched in the mesoderm and dorsal ectoderm of early gastrulae. Expression in gastrulae is an early response to FGF signalling. Transcripts for lpar6 are enriched in the neural plate of Xenopus neurulae and loss of function caused forebrain defects, with reduced expression of telencephalic markers (foxg1, emx1 and nkx2-1)...
February 2014: Development
Barbara Gandolfi, Hasan Alhaddad, Verena K Affolter, Jeffrey Brockman, Jens Haggstrom, Shannon E K Joslin, Amanda L Koehne, James C Mullikin, Catherine A Outerbridge, Wesley C Warren, Leslie A Lyons
The cat (Felis silvestris catus) shows significant variation in pelage, morphological, and behavioral phenotypes amongst its over 40 domesticated breeds. The majority of the breed specific phenotypic presentations originated through artificial selection, especially on desired novel phenotypic characteristics that arose only a few hundred years ago. Variations in coat texture and color of hair often delineate breeds amongst domestic animals. Although the genetic basis of several feline coat colors and hair lengths are characterized, less is known about the genes influencing variation in coat growth and texture, especially rexoid - curly coated types...
2013: PloS One
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