Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification
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{"title"=>"Role of UBIAD1 in intracellular cholesterol metabolism and vascular cell calcification", "type"=>"journal", "authors"=>[{"first_name"=>"Sha", "last_name"=>"Liu", "scopus_author_id"=>"56288844800"}, {"first_name"=>"Wang", "last_name"=>"Guo", "scopus_author_id"=>"57169219500"}, {"first_name"=>"Xue", "last_name"=>"Han", "scopus_author_id"=>"55841552100"}, {"first_name"=>"Wendi", "last_name"=>"Dai", "scopus_author_id"=>"53877009900"}, {"first_name"=>"Zongli", "last_name"=>"Diao", "scopus_author_id"=>"56950210800"}, {"first_name"=>"Wenhu", "last_name"=>"Liu", "scopus_author_id"=>"37098845300"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"608829381", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0149639", "sgr"=>"84960934141", "pmid"=>"26890002", "scopus"=>"2-s2.0-84960934141"}, "id"=>"6b658ddf-68a1-3882-854a-4d8d10d56173", "abstract"=>"Vascular calcification is an important risk factor associated with mortality among patients with chronic kidney disease. Intracellular cholesterol metabolism is involved in the process of vascular cell calcification. In this study, we investigated the role of UbiA prenyltransferase domain containing 1 (UBIAD1) in intracellular cholesterol metabolism and vascular cell calcification, and identified its subcellular location. Primary human umbilical vein smooth muscle cells (HUVSMCs) were incubated with either growth medium (1.4 mmol/L Pi) or calcification medium (CM) (3.0 mmol/L Pi). Under treatment with CM, HUVSMCs were further incubated with exogenous cholesterol, or menaquinone-4, a product of UBIAD1. The plasmid and small interfering RNA were transfected in HUVSMCs to alter the expression of UBIAD1. Matrix calcium quantitation, alkaline phosphatase activity, intracellular cholesterol level and menaquinone-4 level were measured. The expression of several genes involved in cholesterol metabolism were analyzed. Using an anti-UBIAD1 antibody, an endoplasmic reticulum marker and a Golgi marker, the subcellular location of UBIAD1 in HUVSMCs was analyzed. CM increased matrix calcium, alkaline phosphatase activity and intracellular cholesterol level, and reduced UBIAD1 expression and menaquinone-4 level. Addition of cholesterol contributed to increased matrix calcification and alkaline phosphatase activity in a dose-dependent manner. Elevated expression of UBIAD1 or menaquinone-4 in HUVSMCs treated with CM significantly reduced intracellular cholesterol level, matrix calcification and alkaline phosphatase activity, but increased menaquinone-4 level. Elevated expression of UBIAD1 or menaquinone-4 reduced the gene expression of sterol regulatory element-binding protein-2, and increased gene expression of ATP binding cassette transporters A1, which are in charge of cholesterol synthesis and efflux. UBIAD1 co-localized with the endoplasmic reticulum marker and the Golgi marker in HUVSMCs. In conclusion, high intracellular cholesterol content contributes to phosphate-induced vascular cell differentiation and calcification. UBIAD1 or menaquinone-4 could decrease vascular cell differentiation and calcification, probably via its potent role of inversely modulating cellular cholesterol.", "link"=>"http://www.mendeley.com/research/role-ubiad1-intracellular-cholesterol-metabolism-vascular-cell-calcification", "reader_count"=>9, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4234402"], "description"=>"<p>Images of the Alizarin Red S staining to show the mineral deposition in matrix of HUVSMCs cultured in GM or CM for 14 d.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587840, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g002", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_CM_on_matrix_calcification_identified_by_Alizarin_Red_S_staining_/2587840", "title"=>"Effects of CM on matrix calcification identified by Alizarin Red S staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/4234447"], "description"=>"<p>(A) UBIAD1 expressed in the cytoplasm of HUVSMCs: (a–b) HUVSMCs transfected with UBIAD1-EGFP plasmid; (c–d) HUVSMCs transfected with EGFP plasmid as control; (e–f) HUVSMCs stained with UBIAD1 antibody and the FITC-conjugated secondary antibody; and (g–h) HUVSMCs stained with the absent UBIAD1 antibody as the negative control. (B) UBIAD1 localized to the ER in HUVSMCs: (a) UBIAD1-EGFP expressed in HUVSMCs; (b and f) the ER marker, ER-tracker red; (c) merged image of a and b; (d) image c with nuclear DAPI staining; (e) HUVSMCs stained with UBIAD1 antibody and the FITC-conjugated secondary antibody; (g) merged image of e and f; (h) image g with nuclear DAPI staining. (C) UBIAD1 localized to the Golgi in HUVSMCs: (a) UBIAD1-EGFP expressed in HUVSMCs; (b and f) the Golgi marker, BODIPY-TR ceramide; (c) merged image of a and b; (d) image c with nuclear DAPI staining; (e) HUVSMCs stained with UBIAD1 antibody and the FITC-conjugated secondary antibody; (g) merged image of e and f; (h) image g with nuclear DAPI staining.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587873, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g009", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/UBIAD1_localizes_to_the_endoplasmic_reticulum_ER_and_the_Golgi_in_HUVSMCs_/2587873", "title"=>"UBIAD1 localizes to the endoplasmic reticulum (ER) and the Golgi in HUVSMCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/4234405"], "description"=>"<p>Matrix calcium (A), ALP activity (B) and intracellular cholesterol (C) increased in a dose-dependent manner in HUVSMCs treated with CM with the addition of cell-permeable cholesterol for 72 h. *<i>P</i> < 0.05, <sup>#</sup><i>P</i> < 0.01, compared with cholesterol 0 μmol/L.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587843, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g003", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_cholesterol_concentration_on_matrix_calcification_and_osteoblastic_differentiation_/2587843", "title"=>"Effects of cholesterol concentration on matrix calcification and osteoblastic differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/4234408"], "description"=>"<p>(A) Endogenous levels of UBIAD1 and β-actin after transfection with siControl or siUBIAD1. (B–E) Differences in matrix calcium (B), ALP activity (C), intracellular cholesterol (D) and MK-4 levels (E) after transfection with siControl or siUBIAD1 in HUVSMCs treated with CM for 72 h. *<i>P</i> < 0.05, <sup>#</sup><i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587846, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Decreased_expression_of_UBIAD1_increased_matrix_calcification_osteoblastic_differentiation_and_intracellular_cholesterol_levels_and_reduced_MK_4_level_/2587846", "title"=>"Decreased expression of UBIAD1 increased matrix calcification, osteoblastic differentiation, and intracellular cholesterol levels and reduced MK-4 level.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/4234411"], "description"=>"<p>(A) Endogenous levels of UBIAD1 and β-actin after transfection with pControl or pUBIAD1. (B–E) Differences in matrix calcium (B), ALP activity (C), intracellular cholesterol (D) and MK-4 level (E) after transfection with pControl or pUBIAD1 in HUVSMCs treated with CM for 72 h. *<i>P</i> < 0.05, <sup>#</sup><i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587849, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g005", "stats"=>{"downloads"=>3, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Elevated_expression_of_UBIAD1_reduced_matrix_calcification_ALP_activity_and_intracellular_cholesterol_levels_and_increased_MK_4_level_/2587849", "title"=>"Elevated expression of UBIAD1 reduced matrix calcification, ALP activity and intracellular cholesterol levels, and increased MK-4 level.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/4234417"], "description"=>"<p>Matrix calcium (A) and ALP activity (B) in HUVSMCs after transfection with pControl or pUBIAD1, with the addition of blank control or cholesterol (CHOL) (25 μmol/L) in HUVSMCs treated with CM for 72 h. *<i>P</i> < 0.05, <sup>#</sup><i>P</i> < 0.01.</p>", "links"=>[], "tags"=>["UBIAD 1", "Golgi marker", "Intracellular Cholesterol Metabolism", "HUVSMC", "intracellular cholesterol level", "gene expression", "ATP binding cassette transporters", "phosphatase activity", "UBIAD 1. Matrix calcium quantitation", "Elevated expression", "cell calcification", "menaquinone", "intracellular cholesterol metabolism", "matrix calcification", "CM", "endoplasmic reticulum marker", "Intracellular cholesterol metabolism", "RNA", "Vascular Cell Calcification Vascular calcification", "UBIAD 1 expression", "intracellular cholesterol content", "UbiA prenyltransferase domain", "subcellular location", "cell differentiation"], "article_id"=>2587855, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Chemical Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Inorganic Chemistry", "Hematology"], "users"=>["Sha Liu", "Wang Guo", "Xue Han", "Wendi Dai", "Zongli Diao", "Wenhu Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149639.g006", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_pUBIAD1_on_matrix_calcification_and_osteoblastic_differentiation_were_attenuated_by_adding_cell_permeable_cholesterol_/2587855", "title"=>"Effects of pUBIAD1 on matrix calcification and osteoblastic differentiation were attenuated by adding cell-permeable cholesterol.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-18 16:16:31"}
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PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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Net::HTTPTooManyRequests

Source
Scopus
Time
2019-08-27 21:07:56 UTC
Target URL
https://api.elsevier.com/content/search/index:SCOPUS?query=DOI(10.1371%2Fjournal.pone.0149639)
Trace

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