caa a22 4500 606235787 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2553-5 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2553-5 Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation [Elektronische Daten] [Guoliang Wang, Ning Ma, Liukun Meng, Yingjie Wei, Jingang Gui] 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. Springer Science+Business Media New York, 2015 Proliferation nationallicence Akt nationallicence Phosphorylation nationallicence Lipocalin-2 (Lcn2) nationallicence Pulmonary hypertension (PH) nationallicence Wang Guoliang Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut Ma Ning Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut Meng Liukun State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China aut Wei Yingjie State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China aut Gui Jingang Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 207-213 0300-8177 410:1-2<207 2015 410 11010 https://doi.org/10.1007/s11010-015-2553-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2553-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Guoliang Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut NATIONALLICENCE 700 1- Ma Ning Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut NATIONALLICENCE 700 1- Meng Liukun State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China aut NATIONALLICENCE 700 1- Wei Yingjie State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China aut NATIONALLICENCE 700 1- Gui Jingang Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children's Hospital, Capital Medical University, 100045, Beijing, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 207-213 0300-8177 410:1-2<207 2015 410 11010