CAJ | 학술논문

目的探讨常染色体显性遗传多囊肾病(ADPKD)中JAK2-STAT3通路对补体因子B(CFB)表达的调控作用.方法收集ADPKD患者肾脏切除术后的肾组织标本,以肾癌根治术患者肾脏切除标本的正常肾脏组织为对照;收集雄性Han:SPRD(Cy/+)大鼠(ADPKD模型)和野生型Han:SPRD(+/+)大鼠4周、8周、16周时的肾组织标本;原代培养16周Han:SPRD(Cy/+)大鼠肾小管上皮细胞,分别给予JAK2抑制剂WP1 066及STAT3抑制剂乙胺嘧啶作用24 h,Western印迹法分别检测Cy/+大鼠、野生型大鼠、ADPKD患者及对照肾组织及各组肾小管上皮细胞中p-JAK2、JAK2、p-STAT3、STAT3、CFB蛋白的表达.结果与对照组相比,ADPKD患者肾组织中p-JAK2、p-STAT3、STAT3、CFB蛋白表达量增加,且差异有统计学意义(均P＜0.05).与野生型大鼠相比,Cy/+大鼠肾组织中p-JAK2、JAK2、p-STAT3、STAT3、CFB蛋白表达量增加且差异有统计学意义(均P＜0.01).细胞实验发现,WP1066抑制Cy/+大鼠肾小管上皮细胞p-JAK2、p-STAT3、CFB蛋白的表达(均P＜0.05),且抑制程度与WP1066剂量相关;乙胺嘧啶抑制Cy/+大鼠肾小管上皮细胞p-STAT3、CFB蛋白的表达(均P＜0.05).结论 ADPKD中JAK2-STAT3通路的异常激活可以促进CFB的表达,并且CFB的蛋白水平与ADPKD的病程相关,其可能参与了ADPKD囊泡的发生和发展.
목적 탐토상염색체현성유전다낭신병(ADPKD)중JAK2-STAT3통로대보체인자B(CFB)표체적조공작용.방법 수집ADPKD환자신장절제술후적신조직표본,이신암근치술환자신장절제표본적정상신장조직위대조;수집웅성Han:SPRD(Cy/+)대서(ADPKD모형)화야생형Han:SPRD(+/+)대서4주、8주、16주시적신조직표본;원대배양16주Han:SPRD(Cy/+)대서신소관상피세포,분별급여JAK2억제제WP1 066급STAT3억제제을알밀정작용24 h,Western인적법분별검측Cy/+대서、야생형대서、ADPKD환자급대조신조직급각조신소관상피세포중p-JAK2、JAK2、p-STAT3、STAT3、CFB단백적표체.결과 여대조조상비,ADPKD환자신조직중p-JAK2、p-STAT3、STAT3、CFB단백표체량증가,차차이유통계학의의(균P＜0.05).여야생형대서상비,Cy/+대서신조직중p-JAK2、JAK2、p-STAT3、STAT3、CFB단백표체량증가차차이유통계학의의(균P＜0.01).세포실험발현,WP1066억제Cy/+대서신소관상피세포p-JAK2、p-STAT3、CFB단백적표체(균P＜0.05),차억제정도여WP1066제량상관;을알밀정억제Cy/+대서신소관상피세포p-STAT3、CFB단백적표체(균P＜0.05).결론 ADPKD중JAK2-STAT3통로적이상격활가이촉진CFB적표체,병차CFB적단백수평여ADPKD적병정상관,기가능삼여료ADPKD낭포적발생화발전.
Objective To investigate the role of JAK2-STAT3 pathway in the expression of complement factor B (CFB) in autosomal dominant polycystic kidney disease (ADPKD).Methods Renal tissue samples of patients with ADPKD after nephrectomy were collected.Normal renal tissue samples as control were taken from patients after radical nephrectomy.Renal tissue samples of Han:SPRD Cy/+ rats (ADPKD model) and wild-type Han:SPRD +/+ rats were also collected at 4,8,16 week.Han:SPRD Cy/+ rat renal tubular epithelial cells (16 w) were primarily cultured in vitro,then stimulated with the JAK2 inhibitor (WP1066) and STAT3 inhibitor (pyrimethamine) for 24 h respectively.Western blotting was used to detect the expression of p-JAK2,JAK2,p-STAT3,STAT3,CFB protein.Results Compared with control group,the protein expressions of p-JAK2,p-STAT3,STAT3,CFB significantly increased in the renal tissue of ADPKD patients (all P ＜ 0.05).The protein expressions of p-JAK2,JAK2,p-STAT3,STAT3 and CFB also significantly increased in the renal tissue of Cy/+ rats compared with wild-type rats (all P ＜ 0.01).When the Cy/+ renal tubular epithelial cells were treated with WP1066,the expressions of p-JAK2,p-STAT3,CFB were suppressed (P ＜ 0.05)and the degree of inhibition was correlated with the WP1066 dose.Pyrimethamine inhibited the protein expressions of p-STAT3 and CFB in the tubular epithelial cells of Cy/+ rats (all P ＜ 0.05) and the degree of inhibition was correlated with the pyrimethamine dose.Conclusions The JAK2-STAT3 pathway is abnormally activated in ADPKD and increases the protein expression of CFB.CFB protein level is correlated with the progress of ADPKD,suggesting that it may take part in the growth and development of ADPKD vesicles.