中华肾病研究电子杂志
中華腎病研究電子雜誌
중화신병연구전자잡지
2013年
6期
310-314
,共5页
糖基化%转化生长因子-β1%肾间质纤维化%机制
糖基化%轉化生長因子-β1%腎間質纖維化%機製
당기화%전화생장인자-β1%신간질섬유화%궤제
Glycosylation%Transforming growth factor-β%Renal tubulointerstitial fibrosis%Mechanism
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。
轉化生長因子-β1（TGF-β）信號通路的激活及蛋白尿是導緻腎間質纖維化的兩箇重要途徑，大連醫科大學腎髒病研究所課題組的研究髮現，糖基化脩飾在二者緻腎間質纖維化過程中髮揮關鍵性的作用。TGFβRII是TGF-β信號通路上的關鍵性受體蛋白，受到覈心巖藻糖基化脩飾，若阻斷瞭它的覈心巖藻糖基化脩飾，則能顯著抑製TGF-β通路的激活，進而抑製TGF-β1導緻的腎小管上皮細胞株-HK-2細胞上皮細胞間充質轉分化（EMT）及單側輸尿管梗阻（UUO）大鼠的腎間質纖維化。在蛋白尿過程中，megalin能通過過度吸收白蛋白促進腎間質纖維化的髮生，它也受到覈心巖藻糖基化的脩飾，若阻斷它的覈心巖藻糖鏈錶達，則能阻斷白蛋白超負荷導緻的HK-2細胞的凋亡及炎癥反應，若高錶達megalin的覈心巖藻糖鏈，能促進細胞的炎癥反應及凋亡。上述研究首次從糖生物學角度闡釋瞭腎間質纖維化進展的新機製。
전화생장인자-β1（TGF-β）신호통로적격활급단백뇨시도치신간질섬유화적량개중요도경，대련의과대학신장병연구소과제조적연구발현，당기화수식재이자치신간질섬유화과정중발휘관건성적작용。TGFβRII시TGF-β신호통로상적관건성수체단백，수도핵심암조당기화수식，약조단료타적핵심암조당기화수식，칙능현저억제TGF-β통로적격활，진이억제TGF-β1도치적신소관상피세포주-HK-2세포상피세포간충질전분화（EMT）급단측수뇨관경조（UUO）대서적신간질섬유화。재단백뇨과정중，megalin능통과과도흡수백단백촉진신간질섬유화적발생，타야수도핵심암조당기화적수식，약조단타적핵심암조당련표체，칙능조단백단백초부하도치적HK-2세포적조망급염증반응，약고표체megalin적핵심암조당련，능촉진세포적염증반응급조망。상술연구수차종당생물학각도천석료신간질섬유화진전적신궤제。
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-βsignaling or proteinuria.TGFβRII,a vital glycoprotein receptor in TGF-βsignaling pathway,is modified by core fucosylation.Blocking the core fucosylation of TGFβRII could significantly inhibit activation of TGF-βsignaling 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.
