Molecular and Cellular Biochemistry

, Volume 410, Issue 1–2, pp 207–213 | Cite as

Activation of the phosphatidylinositol 3-kinase/Akt pathway is involved in lipocalin-2-promoted human pulmonary artery smooth muscle cell proliferation

  • 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.


Proliferation Akt Phosphorylation Lipocalin-2 (Lcn2) Pulmonary hypertension (PH) 



This work was supported by Startup Research Fund by Beijing Children’s Hospital to JG and research grants from the National Natural Science Foundation of China (81170206).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

11010_2015_2553_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (docx 12 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Guoliang Wang
    • 1
    • 2
    • 3
  • Ning Ma
    • 1
  • Liukun Meng
    • 3
  • Yingjie Wei
    • 3
  • Jingang Gui
    • 1
    • 2
  1. 1.Key Laboratory of Major Diseases in Children by Ministry of Education, Beijing Children’s HospitalCapital Medical UniversityBeijingChina
  2. 2.Laboratory of Immunology, Beijing Pediatric Research Institute, Beijing Children’s HospitalCapital Medical UniversityBeijingChina
  3. 3.State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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