Ta Michelle H T, Schwensen Kristina G, Liuwantara David, Huso David L, Watnick Terry, Rangan Gopala K
Michelle HT Ta, Kristina G Schwensen, David Liuwantara, Gopala K Rangan, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, the University of Sydney, Sydney 2145, Australia.
World J Nephrol. 2016 Jul 6;5(4):339-57. doi: 10.5527/wjn.v5.i4.339.
To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD).
The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue.
Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys.
Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
确定多囊肾病（PKD）肾组织中Rel/核因子（NF）-κB蛋白的时间表达及模式。
采用免疫组织化学、免疫荧光和免疫印迹分析，检测出生后3至20周的Lewis多囊肾大鼠（LPK，人类肾单位肾痨-9的基因同源物）肾组织中Rel/NF-κB蛋白的表达。在每个时间点，测定肾脏疾病进展情况以及NF-κB依赖基因（TNFα和CCL2）的mRNA表达。还对人类PKD组织进行了NF-κB的组织学评估。
LPK大鼠肾脏逐渐增大，同时肾细胞增殖增加和间质单核细胞积聚（分别在第3周和第10周达到峰值），以及进行性间质纤维化（与Lewis大鼠肾脏相比，从第3周开始至第6周，α平滑肌肌动蛋白和天狼星红沉积显著增加）。Rel/NF-κB蛋白（磷酸化-p105、p65、p50、c-Rel和RelB）早在出生后第3周就在LPK肾脏的囊性上皮细胞（CEC）中表达，并持续至疾病晚期的第20周。与Lewis大鼠肾脏相比，从第10周开始至第20周，LPK大鼠肾脏中核p65、p50、RelB和细胞质IκBα蛋白水平以及TNFα和CCL2表达上调。NF-κB蛋白在人类PKD的CEC中持续表达。DNA损伤标志物γ-H2AX也在LPK和人类多囊肾的CEC中被鉴定出来。
几种NF-κB蛋白在人类和实验性PKD的CEC中持续表达。这些数据表明，NF-κB信号通路的经典和非经典途径的上调可能是囊性肾病的一种固有且早期的病理特征。
