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Delayed mTOR Inhibition with Low Dose of Everolimus Reduces TGFβ Expression, Attenuates Proteinuria and Renal Damage in the Renal Mass Reduction Model

Publication Date: March 12, 2012
Journal: PLOS ONE
Authors: Melania Kurdián, Inmaculada Herrero Fresneda, Nuria Lloberas, Pepita Gimenez Bonafe, et al
Volume: 7
Issue: 3
Pages: e32516
DOI: https://dx.plos.org/10.1371/journal.pone.0032516
Publisher URL: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0032516
PubMed: http://www.ncbi.nlm.nih.gov/pubmed/22427849
PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299670
Europe PMC: http://europepmc.org/abstract/MED/22427849
Web of Science: 000302381500024
Scopus: 84858011505
Mendeley: http://www.mendeley.com/research/delayed-mtor-inhibition-low-dose-everolimus-reduces-tgf%CE%B2-expression-attenuates-proteinuria-renal-dam

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{"title"=>"Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model", "type"=>"journal", "authors"=>[{"first_name"=>"Melania", "last_name"=>"Kurdián", "scopus_author_id"=>"19234880600"}, {"first_name"=>"Inmaculada", "last_name"=>"Herrero-Fresneda", "scopus_author_id"=>"6603266898"}, {"first_name"=>"Nuria", "last_name"=>"Lloberas", "scopus_author_id"=>"6602858744"}, {"first_name"=>"Pepita", "last_name"=>"Gimenez-Bonafe", "scopus_author_id"=>"6602489637"}, {"first_name"=>"Virginia", "last_name"=>"Coria", "scopus_author_id"=>"55078199500"}, {"first_name"=>"María T.", "last_name"=>"Grande", "scopus_author_id"=>"25951201000"}, {"first_name"=>"José", "last_name"=>"Boggia", "scopus_author_id"=>"35274629700"}, {"first_name"=>"Leonel", "last_name"=>"Malacrida", "scopus_author_id"=>"8066633700"}, {"first_name"=>"Joan", "last_name"=>"Torras", "scopus_author_id"=>"56248458000"}, {"first_name"=>"Miguel A.", "last_name"=>"Arévalo", "scopus_author_id"=>"7006055217"}, {"first_name"=>"Francisco", "last_name"=>"González-Martínez", "scopus_author_id"=>"7004070335"}, {"first_name"=>"José M.", "last_name"=>"López-Novoa", "scopus_author_id"=>"56880472000"}, {"first_name"=>"Josep", "last_name"=>"Grinyó", "scopus_author_id"=>"35399630000"}, {"first_name"=>"Oscar", "last_name"=>"Noboa", "scopus_author_id"=>"6508320271"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"364412875", "sgr"=>"84858011505", "issn"=>"19326203", "pmid"=>"22427849", "scopus"=>"2-s2.0-84858011505", "doi"=>"10.1371/journal.pone.0032516", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"dc92dcd7-513b-3328-8c8a-73a8577a490c", "abstract"=>"BACKGROUND: The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats.\\n\\nMETHODS: This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation.\\n\\nRESULTS: Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model.\\n\\nCONCLUSION: Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.", "link"=>"http://www.mendeley.com/research/delayed-mtor-inhibition-low-dose-everolimus-reduces-tgf%CE%B2-expression-attenuates-proteinuria-renal-dam", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>5, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>6, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Uruguay"=>1}, "group_count"=>0}

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Figshare 39419 Apr 09:03 UTC

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{"files"=>["https://ndownloader.figshare.com/files/668623"], "description"=>"Panel A. Representative images from histological sections stained with Sirius red: Sham Group (A), Control Group (B) and Everolimus Group (C) (magnification 200×). Panel B. Glomerular area (media and SD) and frequency distribution diagram of glomerular area. Panel C. Mesangial fibrosis area (mean and SD) and frequency distribution diagram of mesangial fibrosis area in the three groups. Panel D. Tubulointerstitial fibrosis area (mean and SD) and frequency distribution diagram of tubulointerstitial fibrosis area in the three groups. * p<0.05 vs sham group and †p<0.05 vs control group.", "links"=>[], "tags"=>["glomerular", "hypertrophy", "kidney"], "article_id"=>339093, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.g002", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morphometric_analysis_of_glomerular_hypertrophy_and_kidney_fibrosis_/339093", "title"=>"Morphometric analysis of glomerular hypertrophy and kidney fibrosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:49:06"}
{"files"=>["https://ndownloader.figshare.com/files/668858"], "description"=>"Relative mRNA expression levels of Akt, mTOR and TGF β were assessed by real time quantitative reverse transcriptase-PCR in remnant kidneys of SG (n = 7), CG (n = 5) and EveG (n = 7). *p<0.05 vs sham, **p<0.05 vs CG.", "links"=>[], "tags"=>["mtor", "tgf"], "article_id"=>339330, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_for_Akt_mTOR_and_TGF_946_/339330", "title"=>"mRNA expression for Akt, mTOR and TGF β.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:50:22"}
{"files"=>["https://ndownloader.figshare.com/files/668412"], "description"=>"Representative results from the different groups are shown: Sham Group (A,D,G,J), Control Group (B,E,H,K) and Everolimus Group (C,F,I,L). PAS tinction (A,B,C) (magnification 200×), Immunohistochemistry for α smooth muscle actin (200×) (D,E, F), Glomerular and tubulointerstitial proliferating cell nuclear antigen (PCNA) immunostaining (200×) (G,H,I) and anti CD68 (400×) (J,K,L). Sections were counterstained with eosin.", "links"=>[], "tags"=>["proliferation"], "article_id"=>338864, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.g001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemistry_fibrosis_cell_proliferation_and_inflamation_/338864", "title"=>"Immunohistochemistry: fibrosis, cell proliferation and inflamation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:47:55"}
{"files"=>["https://ndownloader.figshare.com/files/668737"], "description"=>"A) Inmunoblotting analysis for Total Akt 1–2 and phospho-Akt (Ser473); B) Densitometric analysis of pAkt/total Akt: SG (n = 7), CG (n = 5) and EveG (n = 6); C) Inmunoblotting analysis for ERK 1/2 and p-ERK (E-4), D) Densitometric analysis of pERK/total ERK. SG (n = 7), CG (n = 5) and EveG (n = 6). * p<0.05 vs sham group.", "links"=>[], "tags"=>["blot", "abundance"], "article_id"=>339214, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.g003", "stats"=>{"downloads"=>4, "page_views"=>335, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_and_protein_abundance_ratio_for_pAkt_tAkt_and_pERK_tERK_/339214", "title"=>"Western blot and protein abundance ratio for pAkt/tAkt and pERK/tERK.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:49:43"}
{"files"=>["https://ndownloader.figshare.com/files/668951"], "description"=>"Histological and immunohistochemistry semiquantitative analysis.", "links"=>[], "tags"=>["immunohistochemistry", "semiquantitative"], "article_id"=>339420, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.t002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_and_immunohistochemistry_semiquantitative_analysis_/339420", "title"=>"Histological and immunohistochemistry semiquantitative analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 07:50:52"}
{"files"=>["https://ndownloader.figshare.com/files/669008"], "description"=>"Weight, blood pressure, renal function, proteinuria and microalbuminuria from animals at week 8 of treatment.", "links"=>[], "tags"=>["renal", "proteinuria", "microalbuminuria", "animals"], "article_id"=>339477, "categories"=>["Molecular Biology", "Marine Biology", "Immunology"], "users"=>["Melania Kurdián", "Inmaculada Herrero-Fresneda", "Nuria Lloberas", "Pepita Giménez-Bonafé", "Virginia Coria", "María T. Grande", "José Boggia", "Leonel Malacrida", "Joan Torras", "Miguel A. Arévalo", "Francisco González-Martínez", "José M. López-Novoa", "Josep Grinyó", "Oscar Noboa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0032516.t001", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weight_blood_pressure_renal_function_proteinuria_and_microalbuminuria_from_animals_at_week_8_of_treatment_/339477", "title"=>"Weight, blood pressure, renal function, proteinuria and microalbuminuria from animals at week 8 of treatment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 07:51:06"}

PMC Usage Stats 158917 Feb 17:14 UTC

PMC Usage Stats | Further Information

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Relative Metric 19762610 May 16:33 UTC

Relative Metric

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F1000Prime03 Mar 11:50 UTC

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