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Podocyte-derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36.
Munkonda, Mercedes N; Akbari, Shareef; Landry, Chloe; Sun, Suzy; Xiao, Fengxia; Turner, Maddison; Holterman, Chet E; Nasrallah, Rania; Hébert, Richard L; Kennedy, Christopher R J; Burger, Dylan.
Afiliación
  • Munkonda MN; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Akbari S; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Landry C; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Sun S; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Xiao F; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Turner M; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Holterman CE; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Nasrallah R; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Hébert RL; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Kennedy CRJ; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
  • Burger D; Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
J Extracell Vesicles ; 7(1): 1432206, 2018.
Article en En | MEDLINE | ID: mdl-29435202
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses. MPs were isolated from the media of differentiated, untreated human podocytes (hPODs) and administered to cultured human proximal tubule epithelial cells (PTECs). Treatment with podocyte MPs increased p38 and Smad3 phosphorylation and expression of the extracellular matrix (ECM) proteins fibronectin and collagen type IV. MP-induced responses were attenuated by co-treatment with the p38 inhibitor SB202190. A transforming growth factor beta (TGF-ß) receptor inhibitor (LY2109761) blocked MP-induced Smad3 phosphorylation and ECM protein expression but not p38 phosphorylation suggesting that these responses occurred downstream of p38. Finally, blockade of the class B scavenger receptor CD36 completely abrogated MP-mediated p38 phosphorylation, downstream Smad3 activation and fibronectin/collagen type IV induction. Taken together our results suggest that podocyte MPs interact with proximal tubule cells and induce pro-fibrotic responses. Such interactions may contribute to the development of tubular fibrosis in glomerular disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Extracell Vesicles Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Extracell Vesicles Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos