Yang Weiwei, Wang Anning, Zhao Chunling, Li Qinghua, Pan Zhifang, Han Xuefu, Zhang Cuijuan, Wang Guohui, Ji Chao, Wang Guili, Jia Guangtao, Ju Jiyu, Gao Wei, Yu Wenjing, Liu Xiaoying, Chen Xi, Feng Weiguo, Gao Zhiqin, Li Jie, Ren Chune
School of Biological Sciences, Weifang Medical University, Weifang, China.
Biopharmaceutical Laboratory of Health and Family Planning Commission of Shandong Province, Weifang Medical University, Weifang, China.
PLoS One. 2016 Dec 9;11(12):e0166940. doi: 10.1371/journal.pone.0166940. eCollection 2016.
Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. One of the main hallmarks observed in PE is impaired inflammation state. In the current study, we found that miR-125b was deregulated in placental tissues and plasma derived from PE patients, which suggest a potential association between this miRNA and the pathogenesis of PE. Overexpression of miR-125b significantly reduced SGPL1 expression, and luciferase assays confirmed that SGPL1 is a direct target of miR-125b. We also found that miR-125b enhanced IL-8 production by directly targeting sphingosine-1-phosphate lyase 1 (SGPL1), and this effect could be reversed by SGPL1 overexpression. In placentas derived from PE patients, a negative correlation of miR-125b and SGPL1 was observed, and IL-8 was validated to be increased in the circulation of PE patients. Our data demonstrated a critical role of miR-125b in IL-8 production and the development of PE.
子痫前期(PE)是孕产妇和围产儿死亡及发病的主要原因之一。PE中观察到的主要特征之一是炎症状态受损。在本研究中,我们发现miR-125b在PE患者的胎盘组织和血浆中表达失调,这表明该miRNA与PE的发病机制之间可能存在关联。miR-125b的过表达显著降低了SGPL1的表达,荧光素酶测定证实SGPL1是miR-125b的直接靶标。我们还发现miR-125b通过直接靶向鞘氨醇-1-磷酸裂解酶1(SGPL1)增强IL-8的产生,并且这种作用可以通过SGPL1的过表达来逆转。在PE患者的胎盘中,观察到miR-125b与SGPL1呈负相关,并且证实PE患者循环中IL-8增加。我们的数据证明了miR-125b在IL-8产生和PE发展中的关键作用。