Wu, H-T, Kang, L, Su, Y-C, Ou, H-Y, Chan, F-Y, Chen, Y-C, Su, B-H, Wang, Y-S, Wu, C-L, Shiau, A-L and Wu, P (2020) Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes. Clinical Science, 134 (18). 2435 - 2445.

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Abstract

High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide. GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear. In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n=39), compared with the healthy group (n=102), and were positively correlated with Col-1 expression. Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.

Item Type: Article
Uncontrolled Keywords: fibrosis, gestational diabetes, placenta, prothymosin α, trophoblast
Subjects: R Medicine > RC Internal medicine > RC660 Diabetes
Related URLs:
Depositing User: Symplectic
Date Deposited: 05 Oct 2020 16:37
Last Modified: 05 Oct 2020 16:38
URI: https://eprints.keele.ac.uk/id/eprint/8704

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