Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes

Wu

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 a (ProTa) 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 ProTa 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 ProTa transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTa 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 ProTa, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTa overexpression enhanced nuclear factor ?B (NF?B) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NF?B inhibitor reversed the effect of ProTa on fibrosis-related protein expressions. We further investigated whether ProTa is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTa increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTa may be a novel therapeutic target for GDM.

Citation

Wu. (2020). Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes. Clinical Science, 134(18), 2435 - 2445. https://doi.org/10.1042/CS20200147

• Journal Article Type: Article
• Acceptance Date: Sep 10, 2020
• Online Publication Date: Sep 25, 2020
• Publication Date: 2020-09
• Publicly Available Date: May 26, 2023
• Journal: Clinical Science
• Print ISSN: 0143-5221
• Publisher: Portland Press
• Peer Reviewed: Peer Reviewed
• Volume: 134
• Issue: 18
• Pages: 2435 - 2445
• DOI: https://doi.org/10.1042/CS20200147
• Keywords: fibrosis, gestational diabetes, placenta, prothymosin a, trophoblast
• Publisher URL: https://doi.org/10.1042/CS20200147