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21 February 2022 Calpain7 negatively regulates human endometrial stromal cell decidualization in EMs by promoting FoxO1 nuclear exclusion via hydrolyzing AKT1
Nannan Kang, Huizhi Shan, Junxia Wang, Jie Mei, Yue Jiang, Jidong Zhou, Chenyang Huang, Hui Zhang, Mei Zhang, Xin Zhen, Guijun Yan, Haixiang Sun
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Abstract

Endometrial receptivity damage caused by impaired decidualization may be one of the mechanisms of infertility in endometriosis (EMs). Our previous study demonstrated that Calpain-7 (CAPN7) is abnormally overexpressed in EMs. Whether CAPN7 affects the regulation of decidualization and by what mechanism CAPN7 regulates decidualization remains to be determined. In this study, we found CAPN7 expression decreased during human endometrial stromal cell (HESC) decidualization in vitro. CAPN7 negatively regulated decidualization in vitro and in vivo. We also identified one conserved potential PEST sequence in the AKT1 protein and found that CAPN7 was able to hydrolyse AKT1 and enhance AKT1's phosphorylation. Correspondingly, CAPN7 notably promoted the phosphorylation of Forkhead Box O1 (FoxO1), the downstream of AKT1 protein, at Ser319, leading to increased FoxO1 exclusion from nuclei and attenuated FoxO1 transcriptional activity in decidualized HESC. In addition, we detected endometrium CAPN7, p-AKT1, and p-FoxO1 expressions were increased in EMs. These data demonstrate that CAPN7 negatively regulates HESC decidualization in EMs probably by promoting FoxO1's phosphorylation and FoxO1 nuclear exclusion via hydrolyzing AKT1. The dysregulation of CAPN7 may be a novel cause of EMs.

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Nannan Kang, Huizhi Shan, Junxia Wang, Jie Mei, Yue Jiang, Jidong Zhou, Chenyang Huang, Hui Zhang, Mei Zhang, Xin Zhen, Guijun Yan, and Haixiang Sun "Calpain7 negatively regulates human endometrial stromal cell decidualization in EMs by promoting FoxO1 nuclear exclusion via hydrolyzing AKT1," Biology of Reproduction 106(6), 1112-1125, (21 February 2022). https://doi.org/10.1093/biolre/ioac041
Received: 20 October 2021; Accepted: 18 February 2022; Published: 21 February 2022
JOURNAL ARTICLE
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KEYWORDS
AKT1
CAPN7
decidualization
endometriosis
Foxo1
phosphorylation
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