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Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia
Author(s) -
Peng Wei,
Tong Chao,
Li Lei,
Huang Chengyu,
Ran Yuxin,
Chen Xuehai,
Bai Yuxiang,
Liu Yamin,
Zhao Jianlin,
Tan Bin,
Luo Xiaofang,
Wang Hao,
Wen Li,
Zhang Chen,
Zhang Hua,
Ding Yubin,
Qi Hongbo,
Baker Philip N.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802058rr
Subject(s) - trophoblast , placentation , spiral artery , preeclampsia , placenta , cd44 , podosome , andrology , biology , microbiology and biotechnology , cell , chemistry , cancer research , medicine , fetus , pregnancy , biochemistry , genetics , cytoskeleton
ABSTRACT Successful pregnancy requires normal placentation, which largely depends on the tight regulation of proliferation, invasion, and migration of trophoblast cells. Abnormal functioning of trophoblast cells may cause failure of uterine spiral artery remodeling, which may be related to pregnancy‐related disorders, such as preeclampsia. Here, we reported that an actin‐binding protein, α‐actinin (ACTN)4, was dysregulated in placentas from early onset preeclampsia. Moreover, knockdown of ACTN4 markedly inhibited trophoblast cell proliferation by reducing AKT membrane translocation. Furthermore, E‐cadherin regulated ACTN4 and β‐catenin colocalization on trophoblast cell podosomes, and ACTN4 down‐regulation suppressed the E‐cadherin‐induced cell invasion increase via depolymerizing actin filaments. Moreover, loss of ACTN4 recapitulated a number of the features of human preeclampsia. Therefore, our data indicate that ACNT4 plays a role in trophoblast function and is required for normal placental development.—Peng, W., Tong, C., Li, L., Huang, C., Ran, Y., Chen, X., Bai, Y., Liu, Y., Zhao, J., Tan, B., Luo, X., Wang, H., Wen, L., Zhang, C., Zhang, H., Ding, Y., Qi, H., Baker, P. N. Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia. FASEB J. 33, 6327–6338 (2019). www.fasebj.org