TWEAK Activates the Non-Canonical NFκB Pathway in Murine Renal Tubular Cells: Modulation of CCL21
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{"title"=>"TWEAK activates the non-canonical NFκB pathway in murine renal tubular cells: Modulation of CCL21", "type"=>"journal", "authors"=>[{"first_name"=>"Ana B.", "last_name"=>"Sanz", "scopus_author_id"=>"20735486900"}, {"first_name"=>"Maria D.", "last_name"=>"Sanchez-Niño", "scopus_author_id"=>"12774437300"}, {"first_name"=>"Maria C.", "last_name"=>"Izquierdo", "scopus_author_id"=>"7103111868"}, {"first_name"=>"Aniela", "last_name"=>"Jakubowski", "scopus_author_id"=>"7102432018"}, {"first_name"=>"Pilar", "last_name"=>"Justo", "scopus_author_id"=>"6603575331"}, {"first_name"=>"Luis M.", "last_name"=>"Blanco-Colio", "scopus_author_id"=>"6602113538"}, {"first_name"=>"Marta", "last_name"=>"Ruiz-Ortega", "scopus_author_id"=>"7003506378"}, {"first_name"=>"Rafael", "last_name"=>"Selgas", "scopus_author_id"=>"55676515700"}, {"first_name"=>"Jesús", "last_name"=>"Egido", "scopus_author_id"=>"35463099300"}, {"first_name"=>"Alberto", "last_name"=>"Ortiz", "scopus_author_id"=>"7201911399"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-77749282951", "sgr"=>"77749282951", "pui"=>"358424368", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"20126461", "doi"=>"10.1371/journal.pone.0008955"}, "id"=>"8276612a-3d7f-3b6f-9ca9-f86a9ecad219", "abstract"=>"TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control), induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control) and CCL21 protein (2.5+/-0.8-fold over control), which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h). In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control) and CCL21 protein (1.6+/-0.5-fold over control) expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control) or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control). Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control). Our results thus identify TWEAK as a regulator of non-canonical NFkappaB activation and CCL21 expression in tubular cells thus promoting lymphocyte recruitment to the kidney during acute injury.", "link"=>"http://www.mendeley.com/research/tweak-activates-noncanonical-nf%CE%BAb-pathway-murine-renal-tubular-cells-modulation-ccl21", "reader_count"=>34, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>9, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>2, "Other"=>5, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>9, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>2, "Other"=>5, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>9, "Neuroscience"=>2, "Chemistry"=>2, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/865142"], "description"=>"<p><b>A, B</b>) Temporal pattern of nuclear translocation of RelA, RelB and p52 in tubular cells stimulated with TWEAK, (<b>A</b>), or TNFα (<b>B</b>). ELISA of nuclear proteins binding to an oligonucleotide containing the NFκB consensus site. <b>C</b>) Tubular cells were stimulated with 100 ng/mL TWEAK and nuclear cell lysates obtained at various time points were analyzed by Western blot for p52 and RelB. Representative Western blot and densitometric quantification. Mean ± SEM of four independent experiments. *p<0.04 vs control; #p<0.009 vs control. No significant differences were observed between controls at different time points and they were grouped. <b>D</b>) TWEAK induces degradation of the inhibitory subunits IkBα and IkBβ, in a time-course consistent with canonical NFκB pathway activation. Representative western blot of three independent experiments. <b>E</b>) TWEAK induces phosporylation of IKKα subunit of IKK complex. Representative Western blot and quantification of three independent experiments. Mean ± SEM of three experiments. *p<0.05 vs control.</p>", "links"=>[], "tags"=>["translocation", "p52", "relb", "tweak-stimulated", "tubular"], "article_id"=>535587, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g002", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nuclear_translocation_of_p52_and_RelB_in_TWEAK_stimulated_tubular_cells_/535587", "title"=>"Nuclear translocation of p52 and RelB in TWEAK-stimulated tubular cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:51:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/865466"], "description"=>"<p><b>A</b>) RelB and NIK protein levels are efficiently down-regulation by siRNA. Tubular cells were transfected with either a siRNA oligonucleotide targeting RelB, NIK or scrambled control. RelB and NIK expression was assessed 72 hours after transfection by Western blot. Representative Western blot of four independent experiments. <b>B</b>) Tubular cells transfected 72 h earlier were treated with TWEAK for 24 h. RelB or NIK siRNA targeting prevented CCL21 upregulation. Representative Western blot and quantification. Mean ± SEM of four independent experiments. *p<0.02 vs control. #p<0.02 vs scrambled Control + TWEAK.</p>", "links"=>[], "tags"=>["nik", "down-regulation", "sirna", "tweak-induced", "ccl21", "tubular"], "article_id"=>535910, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g005", "stats"=>{"downloads"=>4, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_and_NIK_down_regulation_by_siRNA_reduces_TWEAK_induced_CCL21_expression_in_tubular_cells_/535910", "title"=>"RelB and NIK down-regulation by siRNA reduces TWEAK-induced CCL21 expression in tubular cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:53:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/865686"], "description"=>"<p><b>A</b>) TWEAK treatment of healthy mice increases kidney CCL21a mRNA at 24 h. RNA obtained from the whole kidney. Real time RT-PCR. Mean ±SEM of 6/7 animals per group. *p<0.05 vs control 24 h. <b>B</b>) Increased kidney CCL21 protein induced by TWEAK as assessed by Western blot. Mean ± SEM of 6/7 animals per group. *p<0.05 vs control 24 h. <b>C</b>) CCL21 protein localized to tubular epithelium of kidneys 24 h following TWEAK injection. Original magnification ×200. Detail ×400. Controls for the technique are stained with non-specific IgG. <b>D</b>) Quantification of CCL21 staining as mean ± SEM of 5 animals per group. *p<0.04 vs control.</p>", "links"=>[], "tags"=>["modulates", "kidney", "ccl21"], "article_id"=>536135, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g007", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TWEAK_modulates_kidney_CCL21_expression_in_vivo_/536135", "title"=>"TWEAK modulates kidney CCL21 expression in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:54:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/865557"], "description"=>"<p><b>A</b>) p100/p52 immunohistochemistry 24 h following TWEAK or vehicle injection. Nuclear p52 is observed in renal tubules from mice treated with TWEAK (arrows). Original magnification ×400. Detail ×1000. Pictures representative of 6/7 animals per group. <b>B</b>) RelB immunohistochemistry 24 h following TWEAK or vehicle injection. Nuclear RelB is observed in tubules from mice treated with TWEAK (arrows). Original magnification ×400. Detail ×1000. Controls for the technique are stained with non-specific IgG. Nuclear staining is present in samples stained with specific anti-p100/52 and anti-RelB as compared with the isotype control. Pictures representative of 6/7 animals per group.</p>", "links"=>[], "tags"=>["induces", "translocation", "p52", "relb"], "article_id"=>536009, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g006", "stats"=>{"downloads"=>3, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TWEAK_induces_nuclear_translocation_of_p52_and_RelB_in_vivo_/536009", "title"=>"TWEAK induces nuclear translocation of p52 and RelB in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:53:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/865262"], "description"=>"<p><b>A</b>) Tubular cells pre-treated with 10 µM parthenolide, 10 µM lactacystin or 20 µM MG132 were stimulated with 100 ng/ml TWEAK for 6 h. Mean ± SEM of four experiments. *p<0.0001 vs control; #p<0.02 vs TWEAK alone. Representative Western blots and quantification. <b>B</b>) Treatment with parthenolide does not prevent the nuclear translocation of RelB or p52, whereas lactacystin prevents this nuclear translocation. ELISA of nuclear proteins binding to an oligonucleotide containing the NFκB consensus site. <b>C</b>) Confocal microscopy. TWEAK induced nuclear translocation of RelB and p52 (both in green) at 3 h and 24 h that was prevented by lactacystin but not by parthenolide. TNFα does not induce RelB and p52 (both in green) nuclear translocation at 24 h. Propidium iodide is shown in orange. Note nuclear yellowish color in merged images when the proteins translocate to the nucleus (arrows). Representative pictures of three independent experiments.</p>", "links"=>[], "tags"=>["tweak-induced", "p100"], "article_id"=>535715, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g003", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proteasome_activity_are_required_for_TWEAK_induced_p100_processing_/535715", "title"=>"Proteasome activity are required for TWEAK-induced p100 processing.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:52:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/865379"], "description"=>"<p><b>A</b>) Time-dependent increase in CCL21a, CCL19 and RANTES mRNA expression in tubular cells treated with 100 ng/mL TWEAK or 30 ng/ml TNFα. Real time RT-PCR. Mean ±SEM of four independent experiments. *p<0.04 vs control. <b>B</b>) Time-dependent increase in CCL21 protein expression in tubular cells treated with 100 ng/mL TWEAK or 30 ng/mL TNFα. Mean ±SEM of four independent experiments. *p<0.03 vs control. <b>C</b>) Parthenolide (PTN) does not prevent TWEAK-induced CCL21a mRNA up-regulation at 24 h. Real time RT-PCR. Mean ±SEM of four experiments. *p<0.04 vs control; #p<0.04 vs TWEAK alone. <b>D</b>) Lactacystin prevents TWEAK-induced CCL21a mRNA up-regulation at 24 h. Real time RT-PCR. Mean ±SEM of four experiments. *p<0.04 vs control; #p<0.03 vs TWEAK alone.</p>", "links"=>[], "tags"=>["induces", "ccl21", "tubular"], "article_id"=>535828, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TWEAK_induces_the_expression_of_NF_954_B2_targets_CCL21_and_CCL19_in_tubular_cells_/535828", "title"=>"TWEAK induces the expression of NFκB2 targets, CCL21 and CCL19, in tubular cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:52:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/866148"], "description"=>"<p>The increased number of interstitial lymphocytes stained with anti-CD3 (arrows) in AKI kidneys was reduced by anti-TWEAK antibody treatment or in TWEAK KO mice. Original magnification ×200. Controls for the technique are stained with non-specific Ig. Quantification as mean ± SEM of 6/7 animals per group. *p<0.0001 vs control, #p<0.001 vs AKI, †p<0.002 vs AKI + Isotype IgG.</p>", "links"=>[], "tags"=>["tweak", "decreases", "lymphocytes"], "article_id"=>536597, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g010", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antagonism_or_absence_of_TWEAK_decreases_CD3_lymphocytes_in_AKI_/536597", "title"=>"Antagonism or absence of TWEAK decreases CD3<sup>+</sup> lymphocytes in AKI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:56:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/865851"], "description"=>"<p>AKI was induced by a single folic acid overdose. This model is characterized by increased renal tubular expression of TWEAK and Fn14 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008955#pone.0008955-Sanz1\" target=\"_blank\">[9]</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008955#pone.0008955-Justo2\" target=\"_blank\">[10]</a>. <b>A</b>) RelB immunohistochemistry, <b>B</b>) p52 immunohistochemistry. Note nuclear cell localization of RelB and p52 in mice with acute kidney injury (AKI) at 24 h (arrows). TWEAK deficiency or antibody mediated inhibition decreases RelB and p52 positive nuclei. Controls for the technique are stained with non-specific IgG. Original magnification ×400. Detail ×1000. Pictures representative of 5 animals per group.</p>", "links"=>[], "tags"=>["antagonism", "tweak", "decreases", "relb", "p52", "translocacion"], "article_id"=>536291, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g008", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Absence_or_antagonism_of_TWEAK_decreases_RelB_and_p52_nuclear_translocacion_in_AKI_/536291", "title"=>"Absence or antagonism of TWEAK decreases RelB and p52 nuclear translocacion in AKI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:55:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/864970"], "description"=>"<p><b>A</b>) Time-course of NFκB activation in MCT cells treated with 100 ng/mL TWEAK for indicated time periods. Representative EMSA of four independent experiments. <b>B</b>) Supershift analysis of nuclear extracts from tubular cells treated with TWEAK or TNFα for 24 h. Bands were further separated by the use of a 3% acrylamide gel. Complex 1 consists of two bands (black arrowheads), one containing RelA, which is shared by both cytokines, and another containing RelB and p52, present only in TWEAK-stimulated cells. Bands disappearing in the presence of antibodies marked by empty arrowheads. Representative EMSA of three independent experiments. <b>C,D</b>) Tubular cell lysates were analyzed by Western blot probed with anti-p100/p52. (<b>C</b>) TWEAK time-response. Mean ± SEM of four independent experiments. *p<0.001 vs control; **p<0.0001 vs control. (<b>D</b>) TNFα time-response. Mean ± SEM of three independent experiments. *p<0.02 vs control; **p<0.008 vs control.</p>", "links"=>[], "tags"=>["dna-binding", "complexes", "induced", "tweak", "renal", "tubular"], "article_id"=>535411, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Different_DNA_binding_NF_954_B_complexes_induced_by_TWEAK_and_TNF_945_in_renal_tubular_cells_/535411", "title"=>"Different DNA-binding NFκB complexes induced by TWEAK and TNFα in renal tubular cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:50:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/866020"], "description"=>"<p><b>A</b>) TWEAK deficiency or anti-TWEAK antibodies decrease kidney CCL21a mRNA in AKI at 24 h following injury. Real time RT-PCR. Mean ±SEM of 6/7 animals per group. *p<0.02 vs control, #p<0.05 vs AKI, †p<0.05 vs AKI + isotype IgG. <b>B</b>) Total kidney CCL21 protein expression in AKI at 24 h following renal injury. Measured by Western blot. Mean ± SEM of 6/7 animals per group. *p<0.03 vs control, #p<0.05 vs AKI, †p<0.05 vs AKI + sotype IgG. Representative Western blot showing CCL21 protein expression in AKI model. <b>C</b>) CCL21 immunohistochemistry. Note epithelial cell localization of increased CCL21 expression in mice with AKI, when compared with healthy control or mice with AKI treated with anti-TWEAK. Original magnification ×200. Detail ×400. Controls for the technique are stained with non-specific IgG. <b>D</b>) Quantification of CCL21 as mean ± SEM of 6/7 animals per group. *p<0.004 vs control, #p<0.002 vs AKI.</p>", "links"=>[], "tags"=>["antagonism", "tweak", "decreases", "ccl21"], "article_id"=>536467, "categories"=>["Immunology", "Medicine"], "users"=>["Ana B. Sanz", "Maria D. Sanchez-Niño", "Maria C. Izquierdo", "Aniela Jakubowski", "Pilar Justo", "Luis M. Blanco-Colio", "Marta Ruiz-Ortega", "Rafael Selgas", "Jesús Egido", "Alberto Ortiz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008955.g009", "stats"=>{"downloads"=>1, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Absence_or_antagonism_of_TWEAK_decreases_CCL21_in_AKI_/536467", "title"=>"Absence or antagonism of TWEAK decreases CCL21 in AKI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 02:56:13"}

PMC Usage Stats | Further Information

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Relative Metric

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