He Jin, Zhong Xiaoyi, Zhao Lin, Gan Hua
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Clin Exp Nephrol. 2019 Apr;23(4):501-512. doi: 10.1007/s10157-018-1666-z. Epub 2018 Nov 7.
Vascular calcification is common in chronic kidney disease (CKD) patients, while erythropoietin (EPO) is widely used in the treatment of renal anemia in CKD patients, whether there is a link between the two is still not clear.
The primary rat vascular smooth muscle cells (VSMCs) and CKD rats were treated with EPO and the calcium deposition was observed by alizarin red staining, von Kossa staining and calcium quantification. Activation of JAK2/STAT3/BMP-2 axis and NF-κB signaling pathways was investigated by Western blotting.
EPO-induced calcium deposition in VSMCs and significantly potentiated calcification in CKD rats. Furthermore, EPO activated JAK2/STAT3/BMP-2 axis, NF-κB pathway and the pro-calcification effect of EPO was partially blocked by the STAT3 inhibitor (Cryptotanshinone) or NF-κB inhibitor (BAY 11-7082), respectively, in vitro.
EPO could promote VSMCs calcification in vitro and in vivo and this effect may be achieved through the JAK2/STAT3/BMP-2 axis and NF-κB pathway.
血管钙化在慢性肾脏病（CKD）患者中很常见，而促红细胞生成素（EPO）广泛用于治疗CKD患者的肾性贫血，两者之间是否存在关联仍不清楚。
用EPO处理原代大鼠血管平滑肌细胞（VSMCs）和CKD大鼠，通过茜素红染色、冯库萨染色和钙定量观察钙沉积情况。通过蛋白质免疫印迹法研究JAK2/STAT3/BMP-2轴和NF-κB信号通路的激活情况。
EPO诱导VSMCs中的钙沉积，并显著增强CKD大鼠的钙化。此外，EPO激活JAK2/STAT3/BMP-2轴、NF-κB通路，在体外，EPO的促钙化作用分别被STAT3抑制剂（隐丹参酮）或NF-κB抑制剂（BAY 11-7082）部分阻断。
EPO可在体外和体内促进VSMCs钙化，且这种作用可能通过JAK2/STAT3/BMP-2轴和NF-κB通路实现。
