HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:390

Enthalten in:

Cell and tissue research - 390(2022), 2 vom: 28. Nov., Seite 281-292

Sprache:

Englisch

Beteiligte Personen:

Jiang, Peiyue [VerfasserIn]
Ying, Xia [VerfasserIn]
Li, Zhi [VerfasserIn]
Jiang, Ruoan [VerfasserIn]
Zhou, Jinling [VerfasserIn]
Zhang, Mengmeng [VerfasserIn]
Yang, Xiaofu [VerfasserIn]
Zhu, Xiaojun [VerfasserIn]

Links:

Volltext

Themen:

CD31
CYR61
EC 2.7.1.1
EC 2.7.11.1
EC 3.5.1.98
HDAC5
HDAC5 protein, human
Hdac5 protein, mouse
Hdac5 protein, rat
Histone Deacetylases
Journal Article
MTOR
MTOR protein, human
MTOR protein, rat
MicroRNAs
Preeclampsia
TOR Serine-Threonine Kinases
Trophoblast cells

Anmerkungen:

Date Completed 04.11.2022

Date Revised 04.11.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00441-022-03652-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM344203409