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    题名: Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor
    作者: CY, Sun;GH, Young;YT, Hsieh;YH, Chen;MS, Wu;VC, Wu;JH, Lee;CC, Lee
    关键词: EGF;matrix metalloproteinases;nephrotoxicity;signaling;tubule cells;uremia
    日期: 2015-02-10
    上传时间: 2016-01-06 11:06:43 (UTC+8)
    摘要: Indoxyl sulfate and p-cresol sulfate have been suggested to induce kidney tissue remodeling. This study aimed to clarify the molecular mechanisms underlying this tissue remodeling using cultured human proximal renal tubular cells and half-nephrectomized mice treated with indoxyl sulfate or p-cresol sulfate as study models. Molecular docking results suggested that indoxyl sulfate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor. In vitro spectrophotometric analysis revealed that the presence of a synthetic EGF receptor peptide significantly decreased the spectrophotometric absorption of indoxyl sulfate and p-cresol sulfate. In cultured cells, indoxyl sulfate and p-cresol sulfate activated the EGF receptor and downstream signaling by enhancing receptor dimerization, and increased expression of matrix metalloproteinases 2 and 9 in an EGF receptor-dependent manner. Treatment of mice with indoxyl sulfate or p-cresol sulfate significantly activated the renal EGF receptor and increased the tubulointerstitial expression of matrix metalloproteinases 2 and 9. In conclusion, indoxyl sulfate and p-cresol sulfate may induce kidney tissue remodeling through direct binding and activation of the renal EGF receptor.
    關聯: Journal of the American Society of Nephrology 26(2), pp.281-290
    DOI: 10.1681/ASN.2014010021
    显示于类别:[化學學系暨研究所] 期刊論文

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