Abstract
Our study was to pinpoint the significance of histone deacetylase 5 (HDAC5) affecting the pathogenesis of preeclampsia (PE) via CD31/mammalian target of rapamycin (mTOR) axis by regulating cysteine-rich angiogenic inducer 61 (CYR61). Expression of HDAC5, CYR61, and CD31/mTOR in placental tissues of patients with PE and trophoblast cells HTR-8/SVneo cells was determined first followed by their interaction analysis. Following different transfection, the significance of HDAC5 in cell functions was assayed in relation to CYR61 and CD31/mTOR. An in vivo PE mouse model was constructed for further validation. The clinical tissue and in vitro cell experimentations discovered that HDAC5 was downregulated in placental tissues of PE patients and trophoblast cells, while CYR61, CD31, mTOR, and p-mTOR displayed upregulation. After overexpression of HDAC5, trophoblast cell functions were enhanced. HDAC5 reduced the acetylation enrichment of H3K27 to inhibit the expression of CYR61. Furthermore, CYR61 promoted the activation of CD31/mTOR axis, thereby inhibiting HTR-8/SVneo cell functions. The in vivo rat model confirmed the above alterations. Taken together, HDAC5 contributes to downregulation of CYR61 through histone deacetylation, inactivating CD31/mTOR axis, which prevents the occurrence and development of PE.
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This study was supported by Research Fund Project of Zhejiang Province Traditional Chinese Medicine Science and Technology Plan (No. 2016ZA133).
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Peiyue Jiang, Xia Ying, Zhi Li, and Ruoan Jiang designed the study. Jinling Zhou collated the data, designed and developed the database, carried out data analyses, and produced the initial draft of the manuscript. Mengmeng Zhang, Xiaofu Yang, and Xiaojun Zhu contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.
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Jiang, P., Ying, X., Li, Z. et al. HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia. Cell Tissue Res 390, 281–292 (2022). https://doi.org/10.1007/s00441-022-03652-7
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DOI: https://doi.org/10.1007/s00441-022-03652-7