Overexpression of Apolipoprotein A1 in the Lung Abrogates Fibrosis in Experimental Silicosis
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{"title"=>"Overexpression of Apolipoprotein A1 in the Lung Abrogates Fibrosis in Experimental Silicosis", "type"=>"journal", "authors"=>[{"first_name"=>"Eun hee", "last_name"=>"Lee", "scopus_author_id"=>"57199433006"}, {"first_name"=>"Eun ju", "last_name"=>"Lee", "scopus_author_id"=>"57199433051"}, {"first_name"=>"Hee jeong", "last_name"=>"Kim", "scopus_author_id"=>"55810541800"}, {"first_name"=>"An soo", "last_name"=>"Jang", "scopus_author_id"=>"7004582727"}, {"first_name"=>"Eun suk", "last_name"=>"Koh", "scopus_author_id"=>"55587211200"}, {"first_name"=>"Soo taek", "last_name"=>"Uh", "scopus_author_id"=>"7003335962"}, {"first_name"=>"Yong hoon", "last_name"=>"Kim", "scopus_author_id"=>"56222896600"}, {"first_name"=>"Sung woo", "last_name"=>"Park", "scopus_author_id"=>"56134969600"}, {"first_name"=>"Choon sik", "last_name"=>"Park", "scopus_author_id"=>"7408415097"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"368325908", "doi"=>"10.1371/journal.pone.0055827", "sgr"=>"84873627511", "scopus"=>"2-s2.0-84873627511", "isbn"=>"19326203", "pmid"=>"23409054"}, "id"=>"fcd97f62-a6ac-3ee5-9b50-b421f2c8f937", "abstract"=>"The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1) protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0). ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group) or day 15 (ApoA1_D15 group). The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.", "link"=>"http://www.mendeley.com/research/overexpression-apolipoprotein-a1-lung-abrogates-fibrosis-experimental-silicosis", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>4, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/491762"], "description"=>"<p>**<i>p</i><0.01 compared with the Silica group (D15 and D30).</p>", "links"=>[], "tags"=>["counts", "bal", "apoa1", "transgenic"], "article_id"=>162272, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_cell_counts_from_the_BAL_fluid_of_ApoA1_transgenic_mice_/162272", "title"=>"Differential cell counts from the BAL fluid of ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:37:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/492224"], "description"=>"<p>(<i>A)</i> Immunoblot analysis showed that active form of caspase-3 protein expression was significantly decreased in the ApoA1_D7 and D15 groups compared with the Silica group. **<i>p</i><0.01 compared with the Silica group (D30). *<i>p</i><0.05 compared with the Silica group (D30). <i>(B)</i> Tissues stained by the TUNEL method were observed at ×100 magnification, and the number of TUNEL-positive cells in a minimum of 20 fields per lung was counted (<i>n</i> = 8 mice/group). **<i>p</i><0.01 compared with the Silica group (D15 and D30).</p>", "links"=>[], "tags"=>["silica-induced", "apoptosis", "lungs", "apoa1", "transgenic"], "article_id"=>162732, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_silica_induced_apoptosis_in_the_lungs_of_the_ApoA1_transgenic_mice_/162732", "title"=>"Quantification of silica-induced apoptosis in the lungs of the ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:45:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/492055"], "description"=>"<p>*<i>p</i><0.05 compared with the Silica group (D30).</p>", "links"=>[], "tags"=>["lxa4", "levels", "bal", "apoa1", "transgenic"], "article_id"=>162567, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g005", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_LXA4_levels_in_the_lung_parenchyma_A_and_BAL_fluid_B_of_the_ApoA1_transgenic_mice_/162567", "title"=>"Quantification of LXA4 levels in the lung parenchyma(A) and BAL fluid(B) of the ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:42:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/492322"], "description"=>"<p>IL-1β <i>(A)</i>, TNF-α <i>(B)</i>, KC <i>(C)</i>, MCP-1 <i>(D)</i> and MIP-2 <i>(E)</i> mRNA expression were measured by real-time PCR. *<i>p</i><0.05 compared with the Silica group (D30).</p>", "links"=>[], "tags"=>["proinflammatory", "mediator", "mrnas", "lungs", "apoa1", "transgenic"], "article_id"=>162830, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g007", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Levels_of_proinflammatory_mediator_mRNAs_in_the_lungs_of_ApoA1_transgenic_mice_/162830", "title"=>"Levels of proinflammatory mediator mRNAs in the lungs of ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:47:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/491937"], "description"=>"<p>(<i>A)</i> Masson’s trichrome staining of lung sections. Scale bar = 20 µm. (<i>B)</i> Soluble lung collagen was measured using a Sircol assay. **<i>p<</i>0.01 compared with the Silica group (D15 and D30). (<i>C)</i> The level of the active TGF-b1 in the lung was measured by ELISA. **<i>p</i><0.01 compared with the Silica group (D15 and D30).</p>", "links"=>[], "tags"=>["collagen", "tgf", "levels", "apoa1", "transgenic"], "article_id"=>162446, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantification_of_the_lung_collagen_and_TGF_levels_in_the_ApoA1_transgenic_mice_/162446", "title"=>"Quantification of the lung collagen and TGF levels in the ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:40:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/491612"], "description"=>"<p>(<i>A)</i> Silica was administered via the trachea to ApoA1 transgenic mice (6 to 8 weeks old) on day 0. The mice were given drinking water containing doxycycline to induce hApoA1 overexpression beginning on day 7 (ApoA1_D7 group) or 15 (ApoA1_D15 group) and continuing throughout the experiment. A third group of silica-treated transgenic mice, which received drinking water with no doxycycline during the experiment (Silica group), were sacrificed 7, 15, or 30 days after silica administration. The ApoA1_D7 and D15 mice were sacrificed 30 days after silica administration. (<i>B)</i> Hematoxylin and eosin staining of lung sections from the transgenic mice following silica administration and doxycycline treatment on day 7 (ApoA1_D7) or 15 (ApoA1_D15), and in those that received no doxycycline treatment (Silica group). Silica group D7, D15, and D30 correspond to mice sacrificed 7 (D7), 15 (D15), or 30 days (D30) after silica administration, respectively. Scale bar = 100 µm. (<i>C)</i> Quantification of the area occupied by silicotic nodules in the lung (<i>n</i> = 8/group). **<i>p<</i>0.01 compared with the Silica group (D30). (<i>D)</i> Polarizing light microscopic analysis showed silica particles in the alveolar space in the lungs of the Silica, ApoA1_D7, and ApoA1_D15 group mice. Scale bar = 20 µm. (<i>E)</i> Numbers of silica particles were observed at ×100 magnification using polarizing microscopy, and the number of silica particles in 20 fields per lung was counted (<i>n</i> = 8 mice/group).</p>", "links"=>[], "tags"=>["histological", "tissues", "apoa1", "transgenic"], "article_id"=>162122, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_protocol_and_histological_analysis_of_lung_tissues_from_ApoA1_transgenic_mice_/162122", "title"=>"Experimental protocol and histological analysis of lung tissues from ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:35:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/491474"], "description"=>"<p>Overexpression of hApoA1 was induced using doxycycline-containing drinking water (Doxy+). Control mice were offered normal water (Doxy−). (<i>A)</i> RT-PCR analysis revealed hApoA1 mRNA only in the lungs of mice treated with doxycycline. (<i>B)</i> ApoA1 protein expression was significantly greater in the lungs of doxycycline-treated transgenic mice compared with those of wild-type or transgenic mice not treated with doxycycline (<i>n</i> = 6 mice/group). **<i>p<</i>0.01 compared with WT or Doxy(−) mice. (C) Detection of human ApoA1 in BAL fluids. ELISA was performed on the first 1-mL fraction of BAL fluid, with a detection limit of 3.13 ng/mL (dashed line). Values below the detection limit were treated as 0 (<i>n</i> = 6 mice/group). **<i>p<</i>0.01 compared with Doxy(−) mice. (D<i>)</i> Immunofluorescence analysis showed that ApoA1 was strongly expressed in the alveolar epithelium (white arrow heads) in the doxycycline-treated transgenic mice. Scale bar = 10 µm. H&E, hematoxylin and eosin.</p>", "links"=>[], "tags"=>["apoa1", "transgenic"], "article_id"=>161985, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055827.g001", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_ApoA1_transgenic_mice_/161985", "title"=>"Generation of ApoA1 transgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-08 00:33:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/484162", "https://ndownloader.figshare.com/files/484164", "https://ndownloader.figshare.com/files/484168"], "description"=>"<div><p>The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1) protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0). ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group) or day 15 (ApoA1_D15 group). The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.</p> </div>", "links"=>[], "tags"=>["overexpression", "apolipoprotein", "a1", "abrogates", "fibrosis", "silicosis"], "article_id"=>156319, "categories"=>["Medicine", "Microbiology", "Immunology"], "users"=>["Eun hee Lee", "Eun-ju Lee", "Hee jeong Kim", "An Soo Jang", "Eun suk Koh", "Soo-Taek Uh", "Yong hoon Kim", "Sung-Woo Park", "Choon-Sik Park"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055827.s001", "https://dx.doi.org/10.1371/journal.pone.0055827.s002", "https://dx.doi.org/10.1371/journal.pone.0055827.s003"], "stats"=>{"downloads"=>4, "page_views"=>51, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Overexpression_of_Apolipoprotein_A1_in_the_Lung_Abrogates_Fibrosis_in_Experimental_Silicosis__/156319", "title"=>"Overexpression of Apolipoprotein A1 in the Lung Abrogates Fibrosis in Experimental Silicosis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-08 01:45:19"}

PMC Usage Stats | Further Information

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Relative Metric

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