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Nuclear factor kappa B inhibition promotes closure of the rat ductus arteriosus (866.8)
Author(s) -
Kajimura Ichige,
Akaike Toru,
Yokoyama Utako,
Ishikawa Yoshihiro,
Minamisawa Susumu
Publication year - 2014
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/fasebj.28.1_supplement.866.8
Subject(s) - prostaglandin e2 , fetus , ductus arteriosus , medicine , endocrinology , forskolin , prostaglandin , signal transduction , downregulation and upregulation , nfkb1 , chemistry , microbiology and biotechnology , stimulation , biology , transcription factor , pregnancy , biochemistry , gene , genetics
Background: The ductus arteriosus(DA) is necessary for fetuses and closes after birth. Patent DA(PDA) often causes serious conditions in premature babies. On the other hand, some patients with congenital heart disease need PDA for living. Prostaglandin E2 (PGE2) is involved in both vasodilation and structural remodeling such as intimal thickening through cAMP pathway. However, DA remodeling is not completely prevented by inhibition of cAMP pathway, suggesting that there is a cAMP‐independent PGE2 signal pathway. Methods and Results: We found the nuclear factor kappa b (NFkB) pathway was activated more in EP4‐stimulated SMCs than in Forskolin‐treated SMCs, which was shown by differential DNA microarray analyses. The NFkB inhibitor IMD‐0354 reduced HA production in EP4‐ stimulated SMCs. DA explants from 19th fetuses were cultured for 48 hours in the presence or absence of IMD‐ 0354. IMD‐0354 treatment facilitated closure of DA explants. When IMD‐ 0354 was injected into 21st rat fetuses, the DA significantly contracted. Furthermore, IMD‐ 0354 constricted the DA dissected from 21st rat fetuses in a dose‐dependent manner. Conclusion: The present data demonstrated that NFkB inhibition facilitated DA closure. NFkB may play a role in a cAMP‐independent PGE2 signal pathway of the rat DA.