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Am J Chin Med ; 45(5): 1075-1092, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28659030

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.


Assuntos
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 , 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
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