Augmenting Autophagy to Treat Acute Kidney Injury during Endotoxemia in Mice
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{"title"=>"Augmenting Autophagy to Treat Acute Kidney Injury during Endotoxemia in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Gina M.", "last_name"=>"Howell", "scopus_author_id"=>"36798404400"}, {"first_name"=>"Hernando", "last_name"=>"Gomez", "scopus_author_id"=>"24334777700"}, {"first_name"=>"Richard D.", "last_name"=>"Collage", "scopus_author_id"=>"36185229600"}, {"first_name"=>"Patricia", "last_name"=>"Loughran", "scopus_author_id"=>"57190981438"}, {"first_name"=>"Xianghong", "last_name"=>"Zhang", "scopus_author_id"=>"55715212600"}, {"first_name"=>"Daniel A.", "last_name"=>"Escobar", "scopus_author_id"=>"55804873600"}, {"first_name"=>"Timothy R.", "last_name"=>"Billiar", "scopus_author_id"=>"35353765300"}, {"first_name"=>"Brian S.", "last_name"=>"Zuckerbraun", "scopus_author_id"=>"6602739165"}, {"first_name"=>"Matthew R.", "last_name"=>"Rosengart", "scopus_author_id"=>"6602116778"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23936035", "doi"=>"10.1371/journal.pone.0069520", "sgr"=>"84880799079", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84880799079", "issn"=>"19326203", "pui"=>"369443267"}, "id"=>"b251c2fa-6fe8-3067-beac-fe3583509e30", "abstract"=>"OBJECTIVE: To determine that 1) an age-dependent loss of inducible autophagy underlies the failure to recover from AKI in older, adult animals during endotoxemia, and 2) pharmacologic induction of autophagy, even after established endotoxemia, is of therapeutic utility in facilitating renal recovery in aged mice.\\n\\nDESIGN: Murine model of endotoxemia and cecal ligation and puncture (CLP) induced acute kidney injury (AKI).\\n\\nSETTING: Academic research laboratory.\\n\\nSUBJECTS: C57Bl/6 mice of 8 (young) and 45 (adult) weeks of age.\\n\\nINTERVENTION: Lipopolysaccharide (1.5 mg/kg), Temsirolimus (5 mg/kg), AICAR (100 mg/kg).\\n\\nMEASUREMENTS AND MAIN RESULTS: Herein we report that diminished autophagy underlies the failure to recover renal function in older adult mice utilizing a murine model of LPS-induced AKI. The administration of the mTOR inhibitor temsirolimus, even after established endotoxemia, induced autophagy and protected against the development of AKI.\\n\\nCONCLUSIONS: These novel results demonstrate a role for autophagy in the context of LPS-induced AKI and support further investigation into like interventions that have potential to alter the natural history of disease.", "link"=>"http://www.mendeley.com/research/augmenting-autophagy-treat-acute-kidney-injury-during-endotoxemia-mice", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>4, "Other"=>3, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>4, "Other"=>3, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>10, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Japan"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1137838"], "description"=>"<p>(a) Time course plots for serum BUN and cystatin concentrations after LPS comparing adult and young mice (n = 8–11 mice per group per timepoint). (b) The effects of LPS on autophagy in the renal cortices of adult and young mice were assessed by immunoblot for LC3b (16KD). Representative blot is shown at 48 h timepoint after LPS from n = 4 experiments (8–9 mice per experiment). Corresponding densitometry compares total LC3b of older aged adult and younger animals exposed to LPS. (c) Immunofluorescent microscopy (20X) of renal cortex in adult and young mice harvested at 48 h after LPS. LC3 (Cy3, red), actin (Alexa488, green), nucleus (Hoechst, blue). Representative images of n = 4 experiments (8 mice per experiment). (d) Transmission electron microscopy (10<sup>5</sup>X) of renal cortex of young and adult mice 48 h after endotoxemia. Inset (5×10<sup>5</sup>X). Representative images of n = 4 experiments (8 mice per experiment). arrowheads, autophagosomes; arrows, autophagolysosomes. Data are means ± s.e.m.; rank sum test.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Renal system", "Renal physiology", "immunology", "immunity", "inflammation", "Clinical research design", "Animal models of disease", "Critical care and emergency medicine", "Acute renal failure", "sepsis", "mice", "non-recovery", "renal", "diminished", "autophagy"], "article_id"=>760403, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gina M. Howell", "Hernando Gomez", "Richard D. Collage", "Patricia Loughran", "Xianghong Zhang", "Daniel A. Escobar", "Timothy R. Billiar", "Brian S. Zuckerbraun", "Matthew R. Rosengart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069520.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adult_mice_exhibit_non_recovery_of_renal_function_and_diminished_autophagy_during_endotoxemia_/760403", "title"=>"Adult mice exhibit non-recovery of renal function and diminished autophagy during endotoxemia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:47:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137841"], "description"=>"<p>Immunofluorescent microscopy (20X) of renal cortex harvested at 48 hours after LPS in young mice from 4 experimental groups: NT siRNA and saline control, VPS34 siRNA and saline control, NT siRNA and LPS, and VPS34 siRNA and LPS. (a) VPS34 (Cy3, red), actin (Alexa488, green), nucleus (Hoechst, blue). Representative images of n = 4 experiments (4 mice per experiment). (b) LC3 (Cy3, red), actin (Alexa488, green), nucleus (Hoechst, blue). Representative images of n = 4 experiments (4 mice per experiment). (c) Immunoblot analysis of renal cortex lysate detecting LC3b (16KD) in untreated mice (lanes 1 and 2) and mice treated with Non-target siRNA and LPS (lanes 3 and 4) or VPS34 siRNA and LPS (lanes 5 and 6). Representative blot is shown at 48 h timepoint after LPS from n = 2 experiments (6 mice per experiment).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Renal system", "Renal physiology", "immunology", "immunity", "inflammation", "Clinical research design", "Animal models of disease", "Critical care and emergency medicine", "Acute renal failure", "sepsis", "vps34", "attenuates", "autophagy", "inhibits", "renal", "mice"], "article_id"=>760406, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gina M. Howell", "Hernando Gomez", "Richard D. Collage", "Patricia Loughran", "Xianghong Zhang", "Daniel A. Escobar", "Timothy R. Billiar", "Brian S. Zuckerbraun", "Matthew R. Rosengart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069520.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_VPS34_attenuates_autophagy_and_inhibits_recovery_of_renal_function_in_young_mice_during_endotoxemia_/760406", "title"=>"Inhibition of VPS34 attenuates autophagy and inhibits recovery of renal function in young mice during endotoxemia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:47:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137844"], "description"=>"<p>(a) Time course plots for serum cystatin and blood urea nitrogen (BUN) concentrations after LPS in adult mice receiving either temsirolimus or diluent control (n = 8–11 mice per group per timepoint). (b) Immunoblot analysis of renal cortex lysate detecting LC3b (16KD) and p-Ser<sup>2448</sup> mTOR (289KD) in mice treated with temsirolimus (lanes 1 and 2), diluent control and LPS (lanes 3–5), or temsirolimus and LPS (lanes 6–8). Representative blot is shown at 48 h timepoint after LPS from n = 4 experiments (8 mice per experiment). Graphs summarizing corresponding density of LC3b and p-Ser<sup>2448</sup> mTOR for each experimental condition. (c) Immunofluorescent microscopy (20X) of renal cortex harvested at 48 hours after LPS in 4 experimental groups: diluent control, temsirolimus, diluent control and LPS, and temsirolimus and LPS. LC3 (Cy3, red), actin (Alexa488, green), nucleus (Hoechst, blue). Representative images of n = 4 experiments (8 mice per experiment). (d) Transmission electron microscopy (10<sup>5</sup>X) of renal cortex harvested at 48 hours after LPS in 4 experimental groups. Inset (5×10<sup>5</sup>X) Representative images of n = 4 experiments (8 mice per experiment). arrowheads, autophagosomes; arrows, autophagolysosomes. (e) Serum cystatin and blood urea nitrogen (BUN) concentrations in adult mice receiving either temsirolimus or diluent control after endotoxemia (n = 8–11 mice per group per timepoint). Abbreviations: TEM, temsirolimus. Data are means ± s.e.m.; rank sum test.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Renal system", "Renal physiology", "immunology", "immunity", "inflammation", "Clinical research design", "Animal models of disease", "Critical care and emergency medicine", "Acute renal failure", "sepsis", "improves", "renal", "autophagy", "mice"], "article_id"=>760407, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gina M. Howell", "Hernando Gomez", "Richard D. Collage", "Patricia Loughran", "Xianghong Zhang", "Daniel A. Escobar", "Timothy R. Billiar", "Brian S. Zuckerbraun", "Matthew R. Rosengart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069520.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Temsirolimus_improves_renal_function_and_increases_renal_autophagy_in_adult_mice_during_endotoxemia_/760407", "title"=>"Temsirolimus improves renal function and increases renal autophagy in adult mice during endotoxemia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:47:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/1137845"], "description"=>"<p>Serum cystatin and blood urea nitrogen (BUN) concentrations after CLP or SHAM operation in adult mice receiving either AICAR or diluent control (n = 6 mice per group per timepoint). Data are means ± s.e.m.; rank sum test.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Renal system", "Renal physiology", "immunology", "immunity", "inflammation", "Clinical research design", "Animal models of disease", "Critical care and emergency medicine", "Acute renal failure", "sepsis", "improves", "renal", "mice"], "article_id"=>760408, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gina M. Howell", "Hernando Gomez", "Richard D. Collage", "Patricia Loughran", "Xianghong Zhang", "Daniel A. Escobar", "Timothy R. Billiar", "Brian S. Zuckerbraun", "Matthew R. Rosengart"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069520.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AICAR_improves_renal_function_in_mice_during_CLP_/760408", "title"=>"AICAR improves renal function in mice during CLP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-30 11:47:59"}

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Relative Metric

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