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中华肾病研究电子杂志 ›› 2013, Vol. 02 ›› Issue (06) : 310 -314. doi: 10.3877/cma.j.issn.2095-3216.2013.06.007

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从糖基化角度看肾间质纤维化的新机制
林洪丽1,(), 王大鹏1   
  1. 1.116011 大连医科大学附属第一医院肾内科
  • 出版日期:2013-12-15
  • 通信作者: 林洪丽
  • 基金资助:
    国家自然科学基金项目(30950027)

New mechanism of renal tubulointerstitial fibrosis in sight of glycosylation

Hong-li LIN1,(), Da-peng WANG1   

  1. 1.Department of Nephrology,First Affiliated Hospital of Dalian Medical University,Dalian 116011,China
  • Published:2013-12-15
  • Corresponding author: Hong-li LIN
引用本文:

林洪丽, 王大鹏. 从糖基化角度看肾间质纤维化的新机制[J/OL]. 中华肾病研究电子杂志, 2013, 02(06): 310-314.

Hong-li LIN, Da-peng WANG. New mechanism of renal tubulointerstitial fibrosis in sight of glycosylation[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2013, 02(06): 310-314.

转化生长因子-β1(TGF-β)信号通路的激活及蛋白尿是导致肾间质纤维化的两个重要途径,大连医科大学肾脏病研究所课题组的研究发现,糖基化修饰在二者致肾间质纤维化过程中发挥关键性的作用。 TGFβRII 是TGF-β 信号通路上的关键性受体蛋白,受到核心岩藻糖基化修饰,若阻断了它的核心岩藻糖基化修饰,则能显著抑制TGF-β 通路的激活,进而抑制TGF-β1 导致的肾小管上皮细胞株-HK-2 细胞上皮细胞间充质转分化(EMT)及单侧输尿管梗阻(UUO)大鼠的肾间质纤维化。 在蛋白尿过程中,megalin 能通过过度吸收白蛋白促进肾间质纤维化的发生,它也受到核心岩藻糖基化的修饰,若阻断它的核心岩藻糖链表达,则能阻断白蛋白超负荷导致的HK-2 细胞的凋亡及炎症反应,若高表达megalin 的核心岩藻糖链,能促进细胞的炎症反应及凋亡。 上述研究首次从糖生物学角度阐释了肾间质纤维化进展的新机制。

Activation of transforming growth factor-β (TGF-β) signaling and proteinuria are two important pathways leading to renal tubulointerstitial fibrosis, Lin et.al from Dalian Medical University found that glycosylation may play a key role in renal tubulointerstitial fibrosis caused by activiatiion of TGF-β signaling or proteinuria. TGFβRII, a vital glycoprotein receptor in TGF-β signaling pathway, is modified by core fucosylation. Blocking the core fucosylation of TGFβRII could significantly inhibit activation of TGF-β signaling pathway, thereby inhibiting both the epithelial mesenchymal transition(EMT) of human kidney-2(HK-2) renal tubular epithelial cells and renal tubulointerstitial fibrosis of unilateral ureteral obstruction(UUO) rats caused by TGF-β1. Megalin receptor, which promotes renal fibrosis through excessive absorption of albumin in proteinuria, can also be modified by core fucosylation. Inhibition of the core fucosylation of megalin could block HK-2 cells apoptosis and inflammation caused by albumin overload,while high expression of core fucosylated megalin promoted cell apoptosis and inflammation. The above studies have for the first time explained the mechanism of renal tubulointerstitial fibrosis progression in sight of glycobiology.

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