Base de dados : MEDLINE
Pesquisa : A05.810.453.324.359.620 [Categoria DeCS]
Referências encontradas : 1522 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 153 ir para página                         

  1 / 1522 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28747378
[Au] Autor:Jha JC; Banal C; Okabe J; Gray SP; Hettige T; Chow BSM; Thallas-Bonke V; De Vos L; Holterman CE; Coughlan MT; Power DA; Skene A; Ekinci EI; Cooper ME; Touyz RM; Kennedy CR; Jandeleit-Dahm K
[Ad] Endereço:JDRF Danielle Alberti Memorial Centre for Diabetic Complications, Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
[Ti] Título:NADPH Oxidase Nox5 Accelerates Renal Injury in Diabetic Nephropathy.
[So] Source:Diabetes;66(10):2691-2703, 2017 10.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NADPH oxidase-derived excessive production of reactive oxygen species (ROS) in the kidney plays a key role in mediating renal injury in diabetes. Pathological changes in diabetes include mesangial expansion and accumulation of extracellular matrix (ECM) leading to glomerulosclerosis. There is a paucity of data about the role of the Nox5 isoform of NADPH oxidase in animal models of diabetic nephropathy since Nox5 is absent in the mouse genome. Thus, we examined the role of Nox5 in human diabetic nephropathy in human mesangial cells and in an inducible human Nox5 transgenic mouse exposed to streptozotocin-induced diabetes. In human kidney biopsies, Nox5 was identified to be expressed in glomeruli, which appeared to be increased in diabetes. Colocalization demonstrated Nox5 expression in mesangial cells. In vitro, silencing of Nox5 in human mesangial cells was associated with attenuation of the hyperglycemia and TGF-ß1-induced enhanced ROS production, increased expression of profibrotic and proinflammatory mediators, and increased TRPC6, PKC-α, and PKC-ß expression. In vivo, vascular smooth muscle cell/mesangial cell-specific overexpression of Nox5 in a mouse model of diabetic nephropathy showed enhanced glomerular ROS production, accelerated glomerulosclerosis, mesangial expansion, and ECM protein (collagen IV and fibronectin) accumulation as well as increased macrophage infiltration and expression of the proinflammatory chemokine MCP-1. Collectively, this study provides evidence of a role for Nox5 and its derived ROS in promoting progression of diabetic nephropathy.
[Mh] Termos MeSH primário: Nefropatias Diabéticas/metabolismo
NADPH Oxidases/metabolismo
[Mh] Termos MeSH secundário: Animais
Western Blotting
Linhagem Celular
Nefropatias Diabéticas/genética
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Inflamação/metabolismo
Rim/metabolismo
Glomérulos Renais/metabolismo
Células Mesangiais/metabolismo
Camundongos
Camundongos Transgênicos
NADPH Oxidases/genética
Proteína Quinase C beta/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Reactive Oxygen Species); EC 1.6.3.- (NADPH Oxidases); EC 2.7.11.13 (Protein Kinase C beta)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.2337/db16-1585


  2 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28943431
[Au] Autor:Chen Y; Peng FF; Jin J; Chen HM; Yu H; Zhang BF
[Ad] Endereço:Department of Biochemistry and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, PR China.
[Ti] Título:Src-mediated ligand release-independent EGFR transactivation involves TGF-ß-induced Smad3 activation in mesangial cells.
[So] Source:Biochem Biophys Res Commun;493(2):914-920, 2017 Nov 18.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A great deal of evidence highlighted the pathophysiologic importance of TGF-ß1/Smad3 pathway in masangial extracellular matrix (ECM) accumulation, but some alternative signaling pathways are also involved. TGF-ß was shown recently to induce rapid and transient epidermal-like growth factor receptor (EGFR) transactivation and subsequent fibronectin expression via heparin-binding epidermal-like growth factors (HB-EGF) release and binding in mesangial cells, which is independent of Smad2 activation. However, whether TGF-ß could induce persistent EGFR transactivation remains to be identified. The present study demonstrates that in addition to transient EGFR transactivation, TGF-ß1 can also induce continuous EGFR transactivation by a non-ligand-dependent pathway in rat mesangial cells. This sustained EGFR transactivation is mainly due to Src kinase-mediated persistent EGFR tyrosine phosphorylation at Y845 rather than Y1173. TGF-ß1-induced early Smad3 phosphorylation is independent of transient EGFR transactivation and ERK1/2 activation initiated by HB-EGF release, whereas Src-mediated chronic EGFR transactivation and ERK1/2 activation participate in Smad3 activation in a relatively modest and delayed manner. Therefore, the present study further clarifies the mechanisms of EGFR transactivation in the TGF-ß-initiated ECM upregulation and raises the possibility that targeting EGFR may provide a viable alternative strategy for inhibiting TGF-ß in chronic kidney disease.
[Mh] Termos MeSH primário: Células Mesangiais/metabolismo
Receptor do Fator de Crescimento Epidérmico/genética
Proteína Smad3/metabolismo
Ativação Transcricional
Fator de Crescimento Transformador beta/metabolismo
Quinases da Família src/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Fosforilação
Ratos Sprague-Dawley
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Madh3 protein, rat); 0 (Smad3 Protein); 0 (Transforming Growth Factor beta); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.2 (CSK tyrosine-protein kinase); EC 2.7.10.2 (src-Family Kinases); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


  3 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28857521
[Au] Autor:Pacic A; Senjug P; Bacalja J; Tisljar M; Horvatic I; Bulimbasic S; Knotek M; Galesic K; Galesic Ljubanovic D
[Ad] Endereço:Arijana Pacic, Department of Pathology and Cytology, Dubrava University Hospital, Av. Gojka Suska 6, 10 000 Zagreb, Croatia, arijanapacic@yahoo.com.
[Ti] Título:IgM as a novel predictor of disease progression in secondary focal segmental glomerulosclerosis.
[So] Source:Croat Med J;58(4):281-291, 2017 Aug 31.
[Is] ISSN:1332-8166
[Cp] País de publicação:Croatia
[La] Idioma:eng
[Ab] Resumo:AIM: To determine the role of immunoglobulin M (IgM) deposits in clinical manifestations, disease outcome, and treatment response of idiopathic and secondary focal segmental glomerulosclerosis (FSGS). METHODS: Kidney biopsy specimens of 171 patients diagnosed with FSGS (primary and secondary) and 50 control patients were retrospectively included in the study. For each patient, clinical and outcome data were obtained and compared to morphological parameters, including immunofluorescence analysis of mesangial IgM and complement 3 (C3) deposits analyzed on kidney biopsy samples. RESULTS: There were significant positive correlations between IgM and C3 deposition in secondary FSGS (P<0.001) and between IgM and mesangial deposits detected by electron microscopy in secondary FSGS (P=0.015), which indicated that higher IgM deposition correlated with higher C3 deposition and mesangial deposits only in secondary FSGS. Patients with secondary FSGS and the deposition of IgM showed inferior renal outcomes at earlier time points in comparison with patients with negative IgM expression (P=0.022). CONCLUSIONS: We detected a positive correlation between IgM and C3 in secondary FSGS. The association between IgM deposition and worse renal outcome in secondary FSGS indicates that IgM may play a role in the progression of this disease.
[Mh] Termos MeSH primário: Glomerulosclerose Segmentar e Focal/imunologia
Imunoglobulina M/metabolismo
Rim/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/metabolismo
Estudos de Casos e Controles
Complemento C3/metabolismo
Progressão da Doença
Feminino
Glomerulosclerose Segmentar e Focal/patologia
Seres Humanos
Rim/patologia
Masculino
Células Mesangiais/metabolismo
Células Mesangiais/patologia
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Complement C3); 0 (Immunoglobulin M)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE


  4 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28815607
[Au] Autor:Waters JP; Richards YC; Skepper JN; Southwood M; Upton PD; Morrell NW; Pober JS; Bradley JR
[Ad] Endereço:Department of Medicine, University of Cambridge, Addenbrooke's Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
[Ti] Título:A 3D tri-culture system reveals that activin receptor-like kinase 5 and connective tissue growth factor drive human glomerulosclerosis.
[So] Source:J Pathol;243(3):390-400, 2017 Nov.
[Is] ISSN:1096-9896
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFß, which has been implicated as an important mediator of glomerulosclerosis. GECs form a lumenized vascular network, which regresses in response to TGFß. MCs respond to TGFß by forming glomerulosclerotic-like nodules with matrix deposition. TGFß treatment of podocytes does not alter cell morphology but increases connective tissue growth factor (CTGF) expression. BMP7 prevents TGFß-induced GEC network regression, whereas TGFß-induced MC nodule formation is prevented by SMAD3 siRNA knockdown or ALK5 inhibitors but not BMP7, and increased phospho-SMAD3 was observed in human glomerulosclerosis. In 3D tri-culture, GECs, podocytes, and MCs form a vascular network in which GECs and podocytes interact intimately within a matrix containing MCs. TGFß treatment induces formation of nodules, but combined inhibition of ALK5 and CTGF is required to prevent TGFß-induced nodule formation in tri-cellular cultures. Identification of therapeutic targets for glomerulosclerosis depends on the 3D culture of all three glomerular cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Fator de Crescimento do Tecido Conjuntivo/metabolismo
Nefropatias Diabéticas/metabolismo
Nefropatias Diabéticas/patologia
Glomérulos Renais/patologia
Proteínas Serina-Treonina Quinases/metabolismo
Receptores de Fatores de Crescimento Transformadores beta/metabolismo
[Mh] Termos MeSH secundário: Matriz Extracelular/metabolismo
Seres Humanos
Nefropatias/patologia
Glomérulos Renais/metabolismo
Células Mesangiais/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CTGF protein, human); 0 (Receptors, Transforming Growth Factor beta); 139568-91-5 (Connective Tissue Growth Factor); EC 2.7.1.11 (TGF-beta type I receptor); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1002/path.4960


  5 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28701517
[Au] Autor:Nagai K; Tominaga T; Ueda S; Shibata E; Tamaki M; Matsuura M; Kishi S; Murakami T; Moriya T; Abe H; Doi T
[Ad] Endereço:Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; and knagai@tokushima-u.ac.jp.
[Ti] Título:Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial Expansion.
[So] Source:J Am Soc Nephrol;28(10):2879-2885, 2017 Oct.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and -smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.
[Mh] Termos MeSH primário: Nefropatias/enzimologia
Células Mesangiais/enzimologia
Complexos Multiproteicos/metabolismo
Proteínas Quinases S6 Ribossômicas/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Animais
Feminino
Seres Humanos
Alvo Mecanístico do Complexo 1 de Rapamicina
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multiprotein Complexes); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2016111196


  6 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28659030
[Au] Autor:Wu XM; Gao YB; Xu LP; Zou DW; Zhu ZY; Wang XL; Yao WJ; Luo LT; Tong Y; Tian NX; Han ZJ; Dang WY
[Ad] Endereço:* Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10, Youanmenwai, Xitoutiao, Fengtai District, Beijing 100069, China.
[Ti] Título:Tongxinluo Inhibits Renal Fibrosis in Diabetic Nephropathy: Involvement of the Suppression of Intercellular Transfer of TGF-[Formula: see text]1-Containing Exosomes from GECs to GMCs.
[So] Source:Am J Chin Med;45(5):1075-1092, 2017.
[Is] ISSN:0192-415X
[Cp] País de publicação:Singapore
[La] Idioma:eng
[Ab] Resumo:Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-[Formula: see text]1-containing exosomes to activate GMCs through the TGF-[Formula: see text]1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-[Formula: see text]1-containing exosomes from GECs to GMCs. In this study, we demonstrate that TXL can inhibit the secretion of TGF-[Formula: see text]1-containing exosomes from HG-treated GECs. Furthermore, exosomes produced by HG induced-GECs treated with TXL cannot trigger GMC activation, proliferation and extracellular matrix (ECM) overproduction both in vitro and in vivo. These results suggest that TXL can prevent the transfer of TGF-[Formula: see text]1 from GECs to GMCs via exosomes, which may be one of the mechanisms of TXL in the treatment of DN.
[Mh] Termos MeSH primário: Comunicação Celular/efeitos dos fármacos
Comunicação Celular/genética
Nefropatias Diabéticas/tratamento farmacológico
Nefropatias Diabéticas/genética
Medicamentos de Ervas Chinesas/farmacologia
Medicamentos de Ervas Chinesas/uso terapêutico
Células Endoteliais/metabolismo
Exoma/genética
Glomérulos Renais/citologia
Rim/patologia
Células Mesangiais/metabolismo
Fitoterapia
Fator de Crescimento Transformador beta1/genética
Fator de Crescimento Transformador beta1/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Nefropatias Diabéticas/patologia
Modelos Animais de Doenças
Fibrose
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 0 (Transforming Growth Factor beta1); 0 (tongxinluo)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1142/S0192415X17500586


  7 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28646076
[Au] Autor:Liu P; Lassén E; Nair V; Berthier CC; Suguro M; Sihlbom C; Kretzler M; Betsholtz C; Haraldsson B; Ju W; Ebefors K; Nyström J
[Ad] Endereço:Department of Physiology, Institute of Neuroscience and Physiology.
[Ti] Título:Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.
[So] Source:J Am Soc Nephrol;28(10):2961-2972, 2017 Oct.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN ( =19) and controls ( =22). Using curated glomerular cell type-specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell-positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell-positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with scores derived from the expression profile of mesangial cell-positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell-positive standard gene score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.
[Mh] Termos MeSH primário: Glomerulonefrite por IGA/metabolismo
Células Mesangiais/metabolismo
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Células Cultivadas
Feminino
Perfilação da Expressão Gênica
Glomerulonefrite por IGA/genética
Seres Humanos
Masculino
Meia-Idade
Proteoma
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteome)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2016101103


  8 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28637791
[Au] Autor:Chaudhari S; Li W; Wang Y; Jiang H; Ma Y; Davis ME; Zuckerman JE; Ma R
[Ad] Endereço:Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center, Fort Worth, Texas.
[Ti] Título:Store-operated calcium entry suppressed the TGF-ß1/Smad3 signaling pathway in glomerular mesangial cells.
[So] Source:Am J Physiol Renal Physiol;313(3):F729-F739, 2017 Sep 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca entry (SOCE) in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGF-ß1 (5 ng/ml for 15 h) significantly increased Smad3 phosphorylation, as evaluated by immunoblot. However, this response was markedly inhibited by thapsigargin (1 µM), a classical activator of store-operated Ca channels. Consistently, both immunocytochemistry and immunoblot showed that TGF-ß1 significantly increased nuclear translocation of Smad3, which was prevented by pretreatment with thapsigargin. Importantly, the thapsigargin effect was reversed by lanthanum (La ; 5 µM) and GSK-7975A (10 µM), both of which are selective blockers of store-operated Ca channels. Furthermore, knockdown of Orai1, the pore-forming subunit of the store-operated Ca channels, significantly augmented TGF-ß1-induced Smad3 phosphorylation. Overexpression of Orai1 augmented the inhibitory effect of thapsigargin on TGF-ß1-induced phosphorylation of Smad3. In agreement with the data from cultured MCs, in vivo knockdown of Orai1 specific to MCs using a targeted nanoparticle small interfering RNA delivery system resulted in a marked increase in abundance of phosphorylated Smad3 and in nuclear translocation of Smad3 in the glomerulus of mice. Taken together, our results indicate that SOCE in MCs negatively regulates the TGF-ß1/Smad3 signaling pathway.
[Mh] Termos MeSH primário: Sinalização do Cálcio
Células Mesangiais/efeitos dos fármacos
Proteína ORAI1/metabolismo
Proteína Smad3/metabolismo
Fator de Crescimento Transformador beta1/farmacologia
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Animais
Bloqueadores dos Canais de Cálcio/farmacologia
Células Cultivadas
Colágeno Tipo IV/metabolismo
Inibidores Enzimáticos/farmacologia
Fibronectinas/metabolismo
Seres Humanos
Masculino
Células Mesangiais/metabolismo
Camundongos Endogâmicos C57BL
Proteína ORAI1/antagonistas & inibidores
Proteína ORAI1/genética
Fosforilação
Interferência de RNA
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (Collagen Type IV); 0 (Enzyme Inhibitors); 0 (Fibronectins); 0 (ORAI1 Protein); 0 (ORAI1 protein, human); 0 (Orai1 protein, mouse); 0 (SMAD3 protein, human); 0 (Smad3 Protein); 0 (Smad3 protein, mouse); 0 (TGFB1 protein, human); 0 (Transforming Growth Factor beta1); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00483.2016


  9 / 1522 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28593583
[Au] Autor:Kitada M; Ogura Y; Monno I; Koya D
[Ad] Endereço:Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. kitta@kanazawa-med.ac.jp.
[Ti] Título:Regulating Autophagy as a Therapeutic Target for Diabetic Nephropathy.
[So] Source:Curr Diab Rep;17(7):53, 2017 Jul.
[Is] ISSN:1539-0829
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE OF REVIEW: Autophagy promotes cellular health in response to various cellular stresses and to changes in nutrient conditions. In this review, we focus on the role of autophagy in the pathogenesis of diabetic nephropathy and discuss the regulation of autophagy as a new therapeutic target for the suppression of diabetic nephropathy. RECENT FINDINGS: Previous studies have indicated that autophagy deficiency or insufficiency in renal cells, including podocytes, mesangial cells, endothelial cells and tubular cells, contributes to the pathogenesis of diabetic nephropathy. Alterations in the nutrient-sensing pathways, including mammalian target of rapamycin complex1 (mTORC1), AMP-activated kinase (AMPK) and Sirt1, due to excess nutrition in diabetes are implicated in the impairment of autophagy. Maintaining both basal and adaptive autophagy against cellular stress may protect the kidney from diabetes-induced cellular stresses. Therefore, the activation of autophagy through the modulation of nutrient-sensing pathways may be a new therapeutic option for the suppression of diabetic nephropathy.
[Mh] Termos MeSH primário: Autofagia
Nefropatias Diabéticas/patologia
[Mh] Termos MeSH secundário: Envelhecimento/patologia
Animais
Seres Humanos
Células Mesangiais/patologia
Modelos Biológicos
Podócitos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1007/s11892-017-0879-y


  10 / 1522 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28549199
[Au] Autor:Zhao D; Zhang CJ; Yang R; Chen JP; Ma L; Liu G; Yang XP
[Ad] Endereço:Department of Nephrology, First Affiliated Hospital, School of Medicine, , , China.
[Ti] Título:Effect of 1,25(OH D on the proliferation of human mesangial cells and their expression of Ki67.
[So] Source:Genet Mol Res;16(2), 2017 May 25.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Previous studies have found that 1,25-dihydroxyvitamin D [1,25(OH) D or VD ] exerts many biological effects, including the inhibition of cell proliferation and induction of apoptosis, but its mechanism of action remains unclear. The goal of our investigation was to explore the effects of 1,25(OH) D on the proliferation of cultured human mesangial cells and their expression of Ki67 in vitro, and to establish its mechanism of action. Cultured human mesangial cells were randomly divided into the following four groups: normal control (N group; administered Dulbecco's modified Eagle's medium containing 5% fetal bovine serum), proliferation [epidermal growth factor (EGF) group; administered 10 µg/L EGF], VD intervention [administered 10 M 1,25(OH) D ], and proliferation and intervention [EGF+VD group; administered 10 µg/L EGF and 10 M 1,25(OH) D ]. Cells were incubated for 48 h with the corresponding treatment, and fluorescence immunocytochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect expression of Ki67 protein and mRNA, respectively. Compared to the N group, Ki67 levels were found to be higher in the EGF group but significantly lower in the VD intervention group. Moreover, expression of Ki67 by cells in the EGF+VD group was significantly lower than that of those in the EGF group. All of these differences were statistically significant (P < 0.05). In conclusion, 1,25(OH) D inhibited Ki67 expression and the proliferation of human mesangial cells; therefore, Ki67 may be regarded as a potent therapeutic target in mesangial proliferative glomerulonephritis.
[Mh] Termos MeSH primário: Proliferação Celular
Células Mesangiais/metabolismo
Vitamina D/análogos & derivados
Vitaminas/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular
Fator de Crescimento Epidérmico/genética
Fator de Crescimento Epidérmico/metabolismo
Seres Humanos
Antígeno Ki-67/genética
Antígeno Ki-67/metabolismo
Células Mesangiais/efeitos dos fármacos
Vitamina D/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ki-67 Antigen); 0 (Vitamins); 1406-16-2 (Vitamin D); 62229-50-9 (Epidermal Growth Factor); 66772-14-3 (1,25-dihydroxyvitamin D)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.4238/gmr16029191



página 1 de 153 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde