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CD142 promotes trophoblast cell migration by inhibiting BCL2-related autophagic degradation of IL-8

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A Correction to this article was published on 29 November 2023

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Abstract

The maintenance of migration of trophoblast cells is beneficial to pregnancy, and its weakening can lead to preeclampsia (PE). CD142 is considered as a classical motility-promoting factor. Our research aimed to explore the role of CD142 in trophoblast cell migration and potential mechanism. Through fluorescence-activated cell sorting (FACS) and gene transduction assays, CD142 expression levels of mouse trophoblast cell lines were upregulated and downregulated respectively. Then, the migratory level was detected through Transwell assays in different groups of trophoblast cells. The corresponding chemokines were screened by ELISA in different sorted trophoblast cells. Based on gene overexpression and knockdown assays, the production mode of identified valuable chemokine was analyzed by detecting gene and protein expression in trophoblast cells. Finally, the contribution of autophagy response to specific chemokine regulated by CD142 was explored by combining different groups of cells and autophagy regulators. Our results showed that both CD142 positive sorting and CD142 overexpression promoted the migratory ability of trophoblast cells, and trophoblast cells with the highest level of CD142 had the strongest migratory ability. In addition, CD142+ cells contained the highest level of IL-8. Consistently, CD142 overexpression promoted IL-8 protein expression in trophoblast cells while CD142 silencing was contrary. However, both CD142 overexpression and CD142 silencing did not affect IL-8 mRNA expression. Moreover, both CD142+ and CD142-overexpressed cells showed higher BCL2 protein expression and poorer autophagic activity. Importantly, autophagy activation with TAT-Beclin1 recovered the increased IL-8 protein expression in CD142+ cells. Obviously, the migratory ability of CD142+ cells inhibited by TAT-Beclin1 was recovered by the addition of IL-8 recombinant factor. In conclusion, CD142 inhibits the degradation of IL-8 through the inhibition of BCL2-Beclin1-autophagy signal transduction, thereby promoting the migration of trophoblast cells.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by The Provincial Natural Science Foundation of China Hainan (819MS119, 821QN395, 822MS167) and The 530 Project of the National Natural Science Foundation of China (2021MSXM02, 2021MSXM12).

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Lei Shi and Linmei Zheng conceived and designed experiments. Linmei Zheng, Rong Tang, and Zhongyi Zhou performed experiments, analyzed data, and prepared figures. Jie Song and Zhicheng Lu assisted in data analysis. Lei Shi and Linmei Zheng wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Lei Shi.

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The authors declare no competing interests.

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Linmei Zheng and Rong Tang are considered as co-first authors.

The original version of this article was revised: The images presented in Fig. 1B in the article as originally published were incorrect and have been replaced by the correct ones.

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Zheng, L., Tang, R., Shi, L. et al. CD142 promotes trophoblast cell migration by inhibiting BCL2-related autophagic degradation of IL-8. In Vitro Cell.Dev.Biol.-Animal 59, 131–141 (2023). https://doi.org/10.1007/s11626-023-00751-9

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  • DOI: https://doi.org/10.1007/s11626-023-00751-9

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