Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway
Posted on 2021-10-14 - 03:27
Abstract Background Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. Several studies have revealed that human chorionic villous mesenchymal stem cells (CV-MSCs) could regulate trophoblasts function. Results To understand how human chorionic villous mesenchymal stem cells (CV-MSCs) regulate trophoblast function, we treated trophoblasts with CV-MSC supernatant under hypoxic conditions. Treatment markedly enhanced proliferation and invasion and augmented autophagy. Transcriptome and pathway analyses of trophoblasts before and after treatment revealed JAK2/STAT3 signalling as an upstream regulator. In addition, STAT3 mRNA and protein levels increased during CV-MSC treatment. Consistent with these findings, JAK2/STAT3 signalling inhibition reduced the autophagy, survival and invasion of trophoblasts, even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, STAT3 overexpression increased autophagy levels in trophoblasts; thus, it positively regulated autophagy in hypoxic trophoblasts. Human placental explants also proved our findings by showing that STAT3 was activated and that LC3B-II levels were increased by CV-MSC treatment. Conclusion In summary, our data suggest that CV-MSC-dependent JAK2/STAT3 signalling activation is a prerequisite for autophagy upregulation in trophoblasts. Graphic abstract
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Chu, Yijing; Zhu, Chengzhan; Yue, Chongyu; Peng, Wei; Chen, Weiping; He, Guifang; et al. (2021). Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5661437.v1
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AUTHORS (14)
YC
Yijing Chu
CZ
Chengzhan Zhu
CY
Chongyu Yue
WP
Wei Peng
WC
Weiping Chen
GH
Guifang He
CL
Changchang Liu
YL
Yang Lv
GG
Guoqiang Gao
KY
Ke Yao
RH
Rendong Han
XH
Xiaoyu Hu
YZ
Yan Zhang
YY
Yuanhua Ye