title: Reduction in placental growth factor impaired gestational beta-cell proliferation through crosstalk between beta-cells and islet endothelial cells.
abstract: Reduced placental growth factor (PLGF) during pregnancy is known to be a reason for developing preeclampsia (PE) and gestational diabetes mellitus (GDM), but the underlying mechanisms remain unclear. Recently, it has been shown that reduced PLGF may induce GDM through suppressing beta-cell mass growth in a PI3k/Akt signalling-dependent manner. Here, we dissected the interaction between beta-cells and islet endothelial cells in this model. We analysed proliferation of beta-cells and islet endothelial cells at different time points of gestation in mice. We cultured mouse islet endothelial cells (MS1), with or without PLGF. We cultured primary mouse beta-cells in conditioned media from PLGF-treated MS1. We cultured MS1 cells in conditioned media from proliferating beta-cells that were activated with conditioned media from PLGF-treated MS1 cells. We analysed cell proliferation by BrdU incorporation. We analysed cell growth by a MTT assay. We found that during mouse gestation, the increases in cell proliferation occurred earlier in beta-cells than in islet endothelial cells. In vitro, PLGF itself failed to induce proliferation of MS1 cells. However, conditioned media from the PLGF-treated MS1 cells induced beta-cell proliferation, resulting in increases in beta-cell number. Moreover, proliferation of MS1 cells significantly increased when MS1 cells were cultured in conditioned media from proliferating beta-cells activated with conditioned media from PLGF-treated MS1 cells. Thus, our data suggest that gestational PLGF may stimulate islet endothelial cells to release growth factors to promote beta-cell proliferation, and proliferating beta-cells in turn release endothelial cell growth factor to increase proliferation of endothelial cells. PE-associated reduction in PLGF impairs these processes to result in islet growth impairment, and subsequently the onset of GDM.
authors.affiliation: Department of Gynecology & Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Gynecology & Obstetrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
keywords: MS1; Preeclampsia; beta-cell proliferation; gestational diabetes mellitus (GDM); placental growth factor (PLGF)