Angiotensin-(1–7) and the G Protein-Coupled Receptor Mas Are Key Players in Renal Inflammation
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{"title"=>"Angiotensin-(1-7) and the G protein-coupled receptor Mas are key players in renal inflammation", "type"=>"journal", "authors"=>[{"first_name"=>"Vanesa", "last_name"=>"Esteban", "scopus_author_id"=>"6701566168"}, {"first_name"=>"Silvia", "last_name"=>"Heringer-Walther", "scopus_author_id"=>"6603300092"}, {"first_name"=>"Anja", "last_name"=>"Sterner-Kock", "scopus_author_id"=>"55891320100"}, {"first_name"=>"Ron", "last_name"=>"de Bruin", "scopus_author_id"=>"7006222983"}, {"first_name"=>"Sandra", "last_name"=>"van den Engel", "scopus_author_id"=>"6508247364"}, {"first_name"=>"Yong", "last_name"=>"Wang", "scopus_author_id"=>"56337058400"}, {"first_name"=>"Sergio", "last_name"=>"Mezzano", "scopus_author_id"=>"7006950828"}, {"first_name"=>"Jesus", "last_name"=>"Egido", "scopus_author_id"=>"35463099300"}, {"first_name"=>"Heinz Peter", "last_name"=>"Schultheiss", "scopus_author_id"=>"16937077800"}, {"first_name"=>"Marta", "last_name"=>"Ruiz-Ortega", "scopus_author_id"=>"7003506378"}, {"first_name"=>"Thomas", "last_name"=>"Walther", "scopus_author_id"=>"7103182985"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"19404405", "doi"=>"10.1371/journal.pone.0005406", "sgr"=>"65549108738", "isbn"=>"1932-6203 (Electronic)", "scopus"=>"2-s2.0-65549108738", "issn"=>"19326203", "pui"=>"354572189"}, "id"=>"89b430aa-782d-3de5-bd71-1d99b86dbf8d", "abstract"=>"Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1-7) by interacting with the G protein-coupled receptor Mas may also have important biological activities.In this study, renal deficiency for Mas diminished renal damage in models of renal insufficiency as unilateral ureteral obstruction and ischemia/reperfusion injury while the infusion of Ang-(1-7) to wild-type mice pronounced the pathological outcome by aggravating the inflammatory response. Mas deficiency inhibited NF-kappaB activation and thus the elevation of inflammation-stimulating cytokines, while Ang-(1-7) infusion had proinflammatory properties in experimental models of renal failure as well as under basal conditions. The Ang-(1-7)-mediated NF-kappaB activation was Mas dependent but did not involve Ang II receptors. Therefore, the blockade of the NF-kappaB-activating properties of the receptor Mas could be a new strategy in the therapy of failing kidney.", "link"=>"http://www.mendeley.com/research/angiotensin17-g-proteincoupled-receptor-mas-key-players-renal-inflammation", "reader_count"=>45, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>17, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>17, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>15, "Agricultural and Biological Sciences"=>16, "Philosophy"=>2, "Neuroscience"=>1, "Business, Management and Accounting"=>1, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Neuroscience"=>{"Neuroscience"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "Philosophy"=>{"Philosophy"=>2}}, "reader_count_by_country"=>{"Colombia"=>1, "United States"=>2}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/898816"], "description"=>"<p>UUO was set in <i>Mas</i>-deficient (Mas−/−) mice and their wild-type controls (Mas+/+), and animals were studied after 2, 5 and 7 days; Masson staining (A) and Azan blue (B) after 2 days and Masson staining after 7 days (C), respectively; magnification: 100×, 200× and 100×, respectively. (D) Shows the quantification of glomeruli with pathomorphological lesions such as collapse, matrix deposition, microthrombi and cellular infiltrates, in UUO kidneys of Mas-deficient mice and their wild-type controls. (E) Demonstrates lower concentrations of blood urea nitrogen in <i>Mas</i>-deficient mice 2 days after UUO. (F) Shows evaluation of apoptosis-related proteins at 2 days of UUO. Data of renal Bax/Bcl-xl ratio expressed as n-fold of increase vs. contralateral kidneys of each genotype, expressed as mean±SEM of 6–8 animals per group. Open and black bars represent Mas+/+ or Mas−/−, respectively; C: contralateral, O: obstructed kidneys; * <i>P</i><0.05 vs. contralateral kidney of its own genotype; # <i>P</i><0.05 vs. Mas+/+ obstructed kidney. (G) Shows the computer analysis of monocytes/macrophages scoring 2, 5 and 7 days of UUO. The presence of inflammatory cell infiltration was determined by immunohistochemistry with anti-F4/80 antibody (specific for monocytes/macrophages; brown staining); magnification: 200×. There were no differences between the number of monocytes/macrophages in contralateral kidneys at 2, 5 and 7 days of UUO (data not shown). Results are expressed as F4/80 positive cells/mm<sup>2</sup> as mean±SEM of 6–10 animals per group. Open bars show data of Mas +/+ and black bars of Mas−/− kidneys, * <i>P</i><0.05 vs. contralateral kidney of the same genotype; # <i>P</i><0.05 vs. Mas+/+ obstructed kidneys; § <i>P</i><0.05 vs. Mas+/+ mice. (H) Illustrates inflammatory cell infiltration in obstructed kidneys (cortex) of Mas+/+ and Mas−/− mice (representative kidneys of 6–10 studied in each genotype, each time point).</p>", "links"=>[], "tags"=>["renal", "lesions", "unilateral", "ureteral", "obstruction", "wild-type"], "article_id"=>569248, "categories"=>["Medicine"], "users"=>["Vanesa Esteban", "Silvia Heringer-Walther", "Anja Sterner-Kock", "Ron de Bruin", "Sandra van den Engel", "Yong Wang", "Sergio Mezzano", "Jesús Egido", "Heinz-Peter Schultheiss", "Marta Ruiz-Ortega", "Thomas Walther"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005406.g001", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_of_renal_lesions_in_the_model_of_unilateral_ureteral_obstruction_UUO_in_Mas_deficient_and_wild_type_mice_/569248", "title"=>"Evolution of renal lesions in the model of unilateral ureteral obstruction (UUO) in <i>Mas</i>-deficient and wild-type mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:01:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/899168"], "description"=>"<p>I/R was performed in wild-type mice infused with saline (I/R Saline) or Ang-(1–7) (I/R Ang-(1–7)) and in mice deficient for Mas (I/R Mas−/−) and their wild-type controls (I/R Mas+/+). Animals were studied 3 days after I/R. Figures A and B show Ladewig and PAS staining respectively of group-representing renal sections. Magnification: 400×. (C) Infiltrating leukocytes were counted based on their morphology and location within renal cortex, medulla, and pelvis in mice infused with saline or Ang-(1–7) and in wild-type (Mas+/+) and Mas-deficient mice (Mas−/−). Renal NF-κB activity after I/R was measured by EMSA (D) and calculated (E) as renal NF-κB activity expressed as n-fold increase vs. wild-type controls and shown as mean±SEM of 6–10 animals per group analyzed in duplicate. ¥ <i>P</i><0.05 vs. saline-infused mice; # <i>P</i><0.05 vs. Mas+/+ mice. The right diagram (F) shows mRNA levels of MCP-1 and IL-6 expressed as n-fold increase vs. wild-type controls and expressed as mean±SEM of 6–8 animals per group analyzed in duplicate. ¥ <i>P</i><0.05 vs. saline-infused mice; # <i>P</i><0.05 vs. Mas+/+ mice.</p>", "links"=>[], "tags"=>["mas", "renal", "lesions"], "article_id"=>569618, "categories"=>["Medicine"], "users"=>["Vanesa Esteban", "Silvia Heringer-Walther", "Anja Sterner-Kock", "Ron de Bruin", "Sandra van den Engel", "Yong Wang", "Sergio Mezzano", "Jesús Egido", "Heinz-Peter Schultheiss", "Marta Ruiz-Ortega", "Thomas Walther"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005406.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_Mas_and_Ang_1_8211_7_on_renal_lesions_in_the_model_of_ischemia_reperfusion_I_R_/569618", "title"=>"Impact of Mas and Ang-(1–7) on renal lesions in the model of ischemia/reperfusion (I/R).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:03:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/899328"], "description"=>"<p><i>Mas</i>-deficient mice (Mas−/−) and mice deficient in all three Ang II receptors (AT1A, AT1B and AT2 = TKO) and their wild-type controls (Mas+/+ and TWT) were infused with Ang-(1–7) or saline for 5 days. Part of the Ang-(1–7)-infused mice were co-treated with the specific Ang-(1–7)-antagonist A779. A shows representative kidney slices stained by anti F4/80 antibody of each group and B summarizes the computer analysis of the monocytes/macrophages score. Results are expressed as F4/80 positive cells/mm<sup>2</sup> as mean±SEM of 6–10 animals per group. (C) NF-κB data of densitometric analysis of EMSA experiments expressed as mean±SEM of 6–10 animals per group analyzed in duplicate were performed in all 4 investigated genotypes under the three different treatment regimes. *<i>P</i><0.05 vs. saline-infused of each genotype, # <i>P</i><0.05 vs Ang-(1–7)-infused Mas+/+. Ŧ <i>P</i><0.05 vs. Ang-(1–7)-infused TWT. ψ <i>P</i><0.05 vs. Ang-(1–7)-infused TKO.</p>", "links"=>[], "tags"=>["induces", "inflammatory", "infiltration", "physiological"], "article_id"=>569772, "categories"=>["Medicine"], "users"=>["Vanesa Esteban", "Silvia Heringer-Walther", "Anja Sterner-Kock", "Ron de Bruin", "Sandra van den Engel", "Yong Wang", "Sergio Mezzano", "Jesús Egido", "Heinz-Peter Schultheiss", "Marta Ruiz-Ortega", "Thomas Walther"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005406.g004", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Angiotensin_1_8211_7_induces_inflammatory_cell_infiltration_under_physiological_conditions_/569772", "title"=>"Angiotensin-(1–7) induces inflammatory cell infiltration under physiological conditions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:03:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/899474"], "description"=>"<p>(A) Growth arrested cells were treated with 10<sup>−7</sup> mol/L Ang-(1–7) and AngII for 1 hour and p65 and p50 subunits were detected by an indirect immunostaining using a mouse FITC-labeled secondary antibody (green staining). Nuclei were stained with propidium iodure (in red). In the merge, the yellow staining shows nuclear localization of the NF-κB proteins after Ang-(1–7) stimulation. The results are representative of 3 independent observations done by confocal microscopy. (B) Growth arrested cells were incubated with 10<sup>−7</sup> mol/L Ang-(1–7), AngII or TNFα for 1 hour. Thereafter, nuclear extracts were isolated and NF-κB activity was determined by binding assay with a labeled NF-κB oligonucleotide and analyzed by EMSA. Data are expressed as an n-fold increase vs. control cells, as mean±SEM of 4 experiments. *<i>P</i><0.05 vs. control. (C) Growth arrested cells were stimulated with 10<sup>−7</sup> mol/L Ang-(1–7) or TNFα for 18 and 24 hours. Gene expression of MCP-1 and IL-6 was analyzed by real-time PCR. Results are expressed as mean±SEM of 4 experiments. *<i>P</i><0.05 vs. control.</p>", "links"=>[], "tags"=>["induces", "localization", "p65", "p50", "proinflammatory", "cytokines", "cultured", "tubuloepithelial"], "article_id"=>569909, "categories"=>["Medicine"], "users"=>["Vanesa Esteban", "Silvia Heringer-Walther", "Anja Sterner-Kock", "Ron de Bruin", "Sandra van den Engel", "Yong Wang", "Sergio Mezzano", "Jesús Egido", "Heinz-Peter Schultheiss", "Marta Ruiz-Ortega", "Thomas Walther"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005406.g005", "stats"=>{"downloads"=>3, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ang_1_8211_7_induces_nuclear_localization_of_p65_and_p50_and_proinflammatory_cytokines_in_cultured_mouse_tubuloepithelial_cells_/569909", "title"=>"Ang-(1–7) induces nuclear localization of p65 and p50 and proinflammatory cytokines in cultured mouse tubuloepithelial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:04:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/898998"], "description"=>"<p>Wild-type mice underwent UUO and were treated with Ang-(1–7) or saline (systemic infusion by osmotic minipumps). (A) A representative western blot showing renal Bax and Bcl-xL expression (upper panel) and the calculation of the Bax/Bcl-xl ratio (lower panel) after 5 days of UUO. Open and black bars represent data of saline- or Ang-(1–7)-infused mice, respectively, expressed as mean±SEM of 6 animals per group. Figures B and C show representative kidney sections (B: cortex with glomerulus; C: medulla) with van Gieson staining and anti-F4/80 immunostaining, respectively (positive immunoreactivity reveals brown signal [arrowheads]). Magnification: 400×. (D) Infiltrating leukocytes were counted based on their morphology and location within renal cortex, medulla, and pelvis in mice infused with saline or Ang-(1–7). (E) Renal NF-κB activation was measured in wild-type mice infused with saline or Ang-(1–7) and in Mas-deficient mice (Mas−/−) and their respective wild-type controls (Mas+/+) at 2 and 5 days of UUO. The figure shows data of renal NF-κB activity expressed as n-fold increase vs. contralateral kidney as mean±SEM of 6 animals per group analyzed in duplicate. (F) Shows a representative EMSA experiment. Competition assay with a 100-fold excess of unlabeled NF-κB shows the specificity of the binding (marked by arrows). The position of free oligonucleotides is indicated. (G) Shows data of gene expression of proinflammatory factors (MCP-1 and IL-6) obtained by real-time PCR experiments and expressed as n-fold increase vs. contralateral kidney as mean±SEM of 8–10 animals per group; C: contralateral, O: obstructed kidneys. * <i>P</i><0.05 vs. contralateral kidney of the same genotype; # <i>P</i><0.05 vs. Mas+/+ obstructed kidney; ¥ <i>P</i><0.05 vs. saline-infused obstructed kidneys.</p>", "links"=>[], "tags"=>["fibrosis", "inflammatory", "processes", "wild-type", "mice", "unilateral", "ureteral", "obstruction"], "article_id"=>569439, "categories"=>["Medicine"], "users"=>["Vanesa Esteban", "Silvia Heringer-Walther", "Anja Sterner-Kock", "Ron de Bruin", "Sandra van den Engel", "Yong Wang", "Sergio Mezzano", "Jesús Egido", "Heinz-Peter Schultheiss", "Marta Ruiz-Ortega", "Thomas Walther"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005406.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_Ang_1_8211_7_treatment_on_apoptosis_fibrosis_and_inflammatory_processes_in_wild_type_mice_with_unilateral_ureteral_obstruction_UUO_/569439", "title"=>"Effect of Ang-(1–7) treatment on apoptosis, fibrosis and inflammatory processes in wild-type mice with unilateral ureteral obstruction (UUO).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:02:10"}

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Relative Metric

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