TY - JOUR
T1 - Fetal lung C4BPA induces p100 processing in human placenta
AU - Ithier, Mayra Cruz
AU - Parobchak, Nataliya
AU - Yadava, Stacy
AU - Cheng, Jerry
AU - Wang, Bingbing
AU - Rosen, Todd
N1 - Funding Information:
The authors wish to thank Dr. Weifeng Liu for his valuable suggestions in selecting mutant residues of C4BPA and structural analysis of C4BPA and CD40. The authors also thank Drs Arnold Rabson and Lisa Denzin for their critical comments on this study, Drs Haiyan Zheng, Caifeng Zhao, and Peter Lobel for technical assistance in proteomics analysis. This study was in part supported by an NIEHS Center grant (ES005022) to B.W.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The non-canonical NF-κB signaling may be a central integrator of a placental clock that governs the length of human pregnancy. We sought to identify fetal signals that could activate this NF-κB pathway in the placenta, and in turn, contribute to the onset of labor. Proteomics analysis of exosomes purified from fetal cord arterial blood revealed a total of 328 proteins, among which 48 were more significantly abundant (p < 0.01) in samples from women who delivered following elective Cesarean-section at term (39 to 40 weeks of estimated gestational age, EGA) compared to those who had elective Cesarean deliveries near term (35 to 36 weeks of EGA). Computational, crystal structural, and gene functional analyses showed that one of these 48 proteins, C4BPA, binds to CD40 of placental villous trophoblast to activate p100 processing to p52, and in turn, pro-labor genes. These results suggest that fetal C4BPA-induced activation of non-canonical NF-κB in human placenta may play a critical role in processes of term or preterm labor.
AB - The non-canonical NF-κB signaling may be a central integrator of a placental clock that governs the length of human pregnancy. We sought to identify fetal signals that could activate this NF-κB pathway in the placenta, and in turn, contribute to the onset of labor. Proteomics analysis of exosomes purified from fetal cord arterial blood revealed a total of 328 proteins, among which 48 were more significantly abundant (p < 0.01) in samples from women who delivered following elective Cesarean-section at term (39 to 40 weeks of estimated gestational age, EGA) compared to those who had elective Cesarean deliveries near term (35 to 36 weeks of EGA). Computational, crystal structural, and gene functional analyses showed that one of these 48 proteins, C4BPA, binds to CD40 of placental villous trophoblast to activate p100 processing to p52, and in turn, pro-labor genes. These results suggest that fetal C4BPA-induced activation of non-canonical NF-κB in human placenta may play a critical role in processes of term or preterm labor.
UR - http://www.scopus.com/inward/record.url?scp=85063726756&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-42078-0
DO - 10.1038/s41598-019-42078-0
M3 - Article
C2 - 30940885
AN - SCOPUS:85063726756
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 5519
ER -