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
Guoliang WangJingang Gui

Abstract

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 th...Continue Reading

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Citations

May 10, 2018·Clinical Science·Mathieu BuonafineFrédéric Jaisser
Jan 22, 2020·Heart and Vessels·Koichiro ShibataTakuya Watanabe
Aug 9, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Michaela JungAnna Sola
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Feb 26, 2019·Journal of Immunology Research·Norie AizawaHidemi Nakagawa
Nov 14, 2019·Cell Reports·Lucie YammineMorgan Gallazzini

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