MicroRNA-21 Knockout Improve the Survival Rate in DSS Induced Fatal Colitis through Protecting against Inflammation and Tissue Injury
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{"title"=>"MicroRNA-21 Knockout Improve the Survival Rate in DSS Induced Fatal Colitis through Protecting against Inflammation and Tissue Injury", "type"=>"journal", "authors"=>[{"first_name"=>"Chenzhang", "last_name"=>"Shi", "scopus_author_id"=>"55213026800"}, {"first_name"=>"Yong", "last_name"=>"Liang", "scopus_author_id"=>"55569183500"}, {"first_name"=>"Jun", "last_name"=>"Yang", "scopus_author_id"=>"56982051300"}, {"first_name"=>"Yang", "last_name"=>"Xia", "scopus_author_id"=>"57129486600"}, {"first_name"=>"Hongqi", "last_name"=>"Chen", "scopus_author_id"=>"36099951400"}, {"first_name"=>"Huazhong", "last_name"=>"Han", "scopus_author_id"=>"55543477600"}, {"first_name"=>"Yongzhi", "last_name"=>"Yang", "scopus_author_id"=>"47661878400"}, {"first_name"=>"Wen", "last_name"=>"Wu", "scopus_author_id"=>"56259109700"}, {"first_name"=>"Renyuan", "last_name"=>"Gao", "scopus_author_id"=>"55581186500"}, {"first_name"=>"Huanlong", "last_name"=>"Qin", "scopus_author_id"=>"7203032006"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23826144", "doi"=>"10.1371/journal.pone.0066814", "sgr"=>"84879476666", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "scopus"=>"2-s2.0-84879476666", "issn"=>"19326203", "pui"=>"369200003"}, "id"=>"4eaaa8b0-fcd0-33bb-a759-b9fcbe485fdc", "abstract"=>"BACKGROUND: MicroRNA-21 (miR-21) is overexpressed in most inflammatory diseases, but its physiological role in gut inflammation and tissue injury is poorly understood. The goal of this work is to understand the role of miR-21 in colitis and damage progression of intestine in a genetically modified murine model.\\n\\nMETHODS: Experimental colitis was induced in miR-21 KO and wild-type (WT) mice by 3.5% dextran sulphate sodium (DSS) administration for 7 days. Disease activity index(DAI), blood parameters, intestinal permeability, histopathologic injury, cytokine and chemokine production, and epithelial cells apoptosis were examined in colons of miR-21 KO and WT mice.\\n\\nRESULTS: miR-21 was overexpressed in intestine of inflammatory bowel diseases (IBD) and acute intestinal obstruction (AIO) patients when compared with normal intestinal tissues. Likewise, miR-21 was up-regulated in colon of IL-10 KO mice when compared with control mice. WT mice rapidly lost weight and were moribund 5 days after treatment with 3.5% DSS, while miR-21 KO mice survived for at least 6 days. Elevated leukocytes and more severe histopathology were observed in WT mice when compared with miR-21 KO mice. Elevated levels of TNF-α and macrophage inflammatory protein-2(MIP-2) in colon culture supernatants from WT mice exhibited significant higher than miR-21 KO mice. Furthermore, CD3 and CD68 positive cells, intestinal permeability and apoptosis of epithelial cells were significantly increased in WT mice when compared with miR-21 KO mice. Finally, we found that miR-21 regulated the intestinal barrier function through modulating the expression of RhoB and CDC42.\\n\\nCONCLUSION: Our results suggest that miR-21 is overexpressed in intestinal inflammation and tissue injury, while knockout of miR-21 in mice improve the survival rate in DSS-induced fatal colitis through protecting against inflammation and tissue injury. Therefore, attenuated expression of miR-21 in gut may prevent the onset or progression of inflammatory bowel disease in patients.", "link"=>"http://www.mendeley.com/research/microrna21-knockout-improve-survival-rate-dss-induced-fatal-colitis-through-protecting-against-infla", "reader_count"=>50, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>13, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Austria"=>1, "Sweden"=>1, "United Kingdom"=>1, "Germany"=>1, "Russia"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1099305"], "description"=>"<p>QRT-PCR were performed to measure the expression of miR-21(A), PDCD4(B), Cdc25A(C), NF-κB(D), Cyclin D1(E), Cdc42 (F), and RhoB (G) in colon of miR-21 KO and WT mice after administration of 3.5% DSS for 7 days.(mean±SEM, n = 6 per group, *p<0.05,***p<0.001, Student’s t test). Meanwhile, we measured the expression of CDC42(H) and RhoB (I) in colon of IL-10 KO and WT mice. (mean±SEM, n = 8 per group, *p<0.05, ***p<0.001, Student’s t test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "mir-21", "ko"], "article_id"=>730125, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g007", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_miR_21_KO_on_expression_of_relevant_gene_/730125", "title"=>"Effects of miR-21 KO on expression of relevant gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099301"], "description"=>"<p>(A) Submucosal swelling, (B) Inflammatory infiltration, and (C) Epithelial injury were assessed for (D) histological colitis. (mean±SEM, n = 5 for miR-21 KO mice and n = 6 for WT mice, *p<0.05, **p<0.01,***p<0.001, Student’s t test). Colon tissue sections from miR-21 KO and WT mice were immunostained with antibodies for (E, F) CD68 and (G, H) CD3 (200×magnification). (I, J) Numbers of positive stained cells were counted per view. (mean±SEM, n = 5 per group, **p<0.01, ***p<0.001, Student’s t test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "ko", "mice", "attenuation", "intestinal", "epithelial", "inflammatory"], "article_id"=>730121, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_21_KO_mice_have_attenuation_in_intestinal_epithelial_injury_and_inflammatory_infiltration_/730121", "title"=>"miR-21 KO mice have attenuation in intestinal epithelial injury and inflammatory infiltration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099298"], "description"=>"<p>(A) Colon weight and (B) Colon length of miR-21 KO and WT mice were measured on day 7 or time of dying following DSS treatment. (mean±SEM, n≥6 per group, *p<0.05, ***p<0.001 by Student’s t test.) (C) Representative images of miR-21 KO and WT colon following of DSS or water treatment. (D) Representative photomicrographs showing epithelial damage and colonic inflammation (H&E stain, 40×magnification, higher magnification photomicrographs on the right×100) in miR-21 KO and WT mice following of DSS or water administration. (E) Representative photomicrographs showing liver damage and inflammation (H&E stain, 400×magnification) in miR-21 KO and WT mice following of DSS or water administration.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "ko", "mice", "attenuation", "severity"], "article_id"=>730118, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_21_KO_mice_have_a_attenuation_in_the_severity_of_DSS_colitis_/730118", "title"=>"miR-21 KO mice have a attenuation in the severity of DSS-colitis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099295"], "description"=>"<p>(A) Red blood cell (RBC) count, (B) Haematocrit, (C) Haemoglobin, and (D) White blood cell (WBC) counts in blood of miR-21 KO and WT mice were measured on 4th day of DSS administration (mean±SEM, n = 6 per group, *p<0.05, **p<0.01,***p<0.001, Student’s t test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "mir-21", "ko", "wt", "mice", "experimentally", "induced"], "article_id"=>730115, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blood_parameters_in_miR_21_KO_and_WT_mice_following_experimentally_induced_colitis_/730115", "title"=>"Blood parameters in miR-21 KO and WT mice following experimentally induced colitis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099294"], "description"=>"<p>MiR-21 KO and WT mice in C57BL/6J background were continuously administered 3.5% dextran sodium sulphate (DSS) freely available in drinking water. (A) Changes in body weights in WT (n = 10) and miR-21 KO (n = 6) mice were measured. (*p<0.05, **p<0.01, ***p<0.001; Student’s t test). Disease severity was measured daily and expressed in terms of (B) body weight loss,(C) fecal blood, (D) diarrhea, and (E) disease activity index (n = 6 per time point for miR-21 KO mice compared with WT control n = 10, *p<0.05, ***p<0.001, Student’s t test). (F) Percentage survival (n = 6 for miR-21 KO mice and n = 10 for WT mice, *p<0.05, log-rank test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "experimentally", "induced", "colitis", "mir-21", "ko"], "article_id"=>730114, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Severe_experimentally_induced_colitis_in_miR_21_KO_mice_/730114", "title"=>"Severe experimentally induced colitis in miR-21 KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099306"], "description"=>"<p>F, Forward; R, Reverse.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "quantitative", "Real-time"], "article_id"=>730126, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primers_Used_for_Quantitative_Real_time_PCR_/730126", "title"=>"Primers Used for Quantitative Real-time PCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099303"], "description"=>"<p>Expression of macrophage inflammatory protein-2 (MIP-2) (A,C)and tumor necrosis factor α (TNF-α) (B,D) in WT and miR-21 KO mice were measured in serum (C,D) and colon culture supernatants (A,B) (mean±SEM, n = 6 per group of DSS treatment, n = 4 per group of water treatment, *p<0.05, **p<0.01,***p<0.001, Student’s t test). (E) <i>In vivo</i> intestinal permeability of WT and miR-21 KO mice before and after DSS treatment were measured by gavage with FITC-Dextran (mean±SEM, n = 5 per group, **p<0.01, ***p<0.001, Student’s t test). Fluorescence micrographs of colons in WT (F, H) and miR-21 KO (G, I) mice stained for terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) (green). The <i>panels</i> are representative of 5 WT and 5 miR-21 KO mice (200×magnification). (J) Apoptotic cells were quantified by counting the apoptotic cells/field. (mean±SEM, n = 5 per group, *p<0.05, ***p<0.001, Student’s t test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "mir-21", "ko", "mucosal", "cytokine", "intestinal", "permeability", "epithelial", "cells", "apoptosis", "dss"], "article_id"=>730123, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_miR_21_KO_on_mucosal_cytokine_production_intestinal_permeability_and_epithelial_cells_apoptosis_before_and_after_DSS_treatment_/730123", "title"=>"Effects of miR-21 KO on mucosal cytokine production, intestinal permeability and epithelial cells apoptosis before and after DSS treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1099293"], "description"=>"<p>(A) Representative photomicrographs in situ detection (200×magnification, n = 3 per group) and (B) QRT-PCR (n = 5 per group) shown miR-21 is overexpressed in intestinal tissue of IBD and AIO patients when compared with normal intestinal tissues (NIT) of human. (C) miR-21 is overexpressed in inflammatory colon tissue of IL-10 KO mice (n = 8) compared with WT mice (n = 8). (D) The expression of miR-21 in colon is significantly increased in DSS-treated WT mice compare to control mice (n = 5 per group). (E) Loss of expression of miR-21 in small intestine and colon of miR-21 KO mice (n = 5) compared with WT mice (n = 5). (F) PCR genotyping of miR-21 KO mice DNAs. (mean±SEM, *p<0.05, **p<0.01,***p<0.001; Student’s t test).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Digestive system", "Digestive physiology", "Biochemistry", "Nucleic acids", "rna", "genetics", "Animal genetics", "Gene function", "Human genetics", "Model organisms", "Animal models", "mouse", "Clinical research design", "Animal models of disease", "Gastroenterology and hepatology", "Inflammatory bowel disease", "mir-21", "inflammation-", "injury-involved", "intestine", "ko"], "article_id"=>730113, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Chenzhang Shi", "Yong Liang", "Jun Yang", "Yang Xia", "Hongqi Chen", "Huazhong Han", "Yongzhi Yang", "Wen Wu", "Renyuan Gao", "Huanlong Qin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066814.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_miR_21_in_inflammation_and_injury_involved_intestine_and_miR_21_KO_mice_/730113", "title"=>"Expression of miR-21 in inflammation- and injury-involved intestine and miR-21 KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-24 03:37:51"}

PMC Usage Stats | Further Information

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Relative Metric

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