Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation
机构：[1]Capital Med Univ, Beijing Childrens Hosp, Key Lab Major Dis Children, Minist Educ, Beijing 100045, Peoples R China;首都医科大学附属北京儿童医院[2]Capital Med Univ, Immunol Lab, Beijing Pediat Res Inst, Beijing Childrens Hosp, Beijing 100045, Peoples R China;科研平台儿科研究所首都医科大学附属北京儿童医院[3]Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China;[4]Peking Union Med Coll, Beijing 100021, Peoples R China
Over-activated PI3K/Akt signaling, a pathway strongly related to cancer survival and proliferation, has been reported recently to be involved in pulmonary artery smooth muscle cell apoptosis and proliferation in pulmonary hypertension (PH). In this study, we observed greatly increased lipocalin-2 (Lcn2) expression accompanied with over-activated PI3K/Akt signaling in a standard rat model of PH induced by monocrotaline. In view of the close relationship between Lcn2 and PI3K/Akt pathway, we hypothesized that the up-regulated Lcn2 might be a trigger of over-activated PI3K/Akt signaling in PH. Our results showed that Lcn2 significantly activated the PI3K/Akt pathway (determined by augmented Akt phosphorylation and up-regulated Mdm2) and significantly promoted proliferation (assessed by Ki67 staining) in cultured human pulmonary artery smooth muscle cells. Furthermore, we demonstrated that inhibition of Akt phosphorylation (LY294002) abrogated the Lcn2-promoted proliferation in cultured human pulmonary artery smooth muscle cells. In conclusion, Lcn2 significantly promoted human pulmonary artery smooth muscle cell proliferation by activating PI3K/Akt pathway. Further study on the role and mechanism of Lcn2 will help explore novel therapeutic strategies based on attenuating over-activated PI3K/Akt signaling in PH.
基金：
Beijing Children's Hospital; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81170206]
第一作者机构：[1]Capital Med Univ, Beijing Childrens Hosp, Key Lab Major Dis Children, Minist Educ, Beijing 100045, Peoples R China;[2]Capital Med Univ, Immunol Lab, Beijing Pediat Res Inst, Beijing Childrens Hosp, Beijing 100045, Peoples R China;[3]Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China;[4]Peking Union Med Coll, Beijing 100021, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Childrens Hosp, Key Lab Major Dis Children, Minist Educ, Beijing 100045, Peoples R China;[2]Capital Med Univ, Immunol Lab, Beijing Pediat Res Inst, Beijing Childrens Hosp, Beijing 100045, Peoples R China;
推荐引用方式(GB/T 7714)：
Wang Guoliang,Ma Ning,Meng Liukun,et al.Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation[J].MOLECULAR AND CELLULAR BIOCHEMISTRY.2015,410(1-2):207-213.doi:10.1007/s11010-015-2553-5.
APA：
Wang, Guoliang,Ma, Ning,Meng, Liukun,Wei, Yingjie&Gui, Jingang.(2015).Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation.MOLECULAR AND CELLULAR BIOCHEMISTRY,410,(1-2)
MLA：
Wang, Guoliang,et al."Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation".MOLECULAR AND CELLULAR BIOCHEMISTRY 410..1-2(2015):207-213
