CCN3 secreted by prostaglandin E2 inhibits intimal cushion formation in the rat ductus arteriosus

Kenji Iwai, Kazumichi Nagasawa, Toru Akaike, Toshio Oshima, Takashi Kato, Susumu Minamisawa

    Research output: Contribution to journalArticle

    Abstract

    The ductus arteriosus (DA), an essential fetal shunt between the pulmonary trunk and the descending aorta, changes its structure during development. Our previous studies have demonstrated that prostaglandin E2 (PGE2)-EP4 signaling promotes intimal cushion formation (ICF) by activating the migration of DA smooth muscle cells via the secretion of hyaluronan. We hypothesized that, in addition to hyaluronan, PGE2 may secrete other proteins that also regulate vascular remodeling in the DA. In order to detect PGE2 stimulation-secreted proteins, we found that CCN3 protein was increased in the culture supernatant in the presence of PGE2 in a dose-dependent manner by nano-flow liquid chromatography coupled with tandem mass spectrometry analysis and enzyme-linked immunosorbent assay. Quantitative RT-PCR analysis revealed that PGE2 stimulation tended to increase the expression levels of CCN3 mRNA in DA smooth muscle cells. Immunohistochemical analysis revealed that CCN3 was highly localized in the entire smooth muscle layers and the endothelium of the DA. Furthermore, exogenous CCN3 inhibited PGE2-induced ICF in the ex vivo DA tissues. These results suggest that CCN3 is a secreted protein of the DA smooth muscle cells induced by PGE2 to suppress ICF of the DA. The present study indicates that CCN3 could be a novel negative regulator of ICF in the DA to fine-tune the PGE2-mediated DA remodeling.

    Original languageEnglish
    Pages (from-to)3242-3247
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume503
    Issue number4
    DOIs
    Publication statusPublished - 2018 Sep 18

    Fingerprint

    Tunica Intima
    Ductus Arteriosus
    Dinoprostone
    Rats
    Muscle
    Cells
    Smooth Muscle Myocytes
    Hyaluronic Acid
    Nephroblastoma Overexpressed Protein
    Immunosorbents
    Proteins
    Liquid chromatography
    Mass spectrometry
    Assays
    Tandem Mass Spectrometry
    Thoracic Aorta
    Liquid Chromatography
    Endothelium
    Smooth Muscle
    Tissue

    Keywords

    • CCN family
    • Ductus arteriosus
    • Mass spectrometry
    • Prostaglandin E
    • Vascular remodeling

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    CCN3 secreted by prostaglandin E2 inhibits intimal cushion formation in the rat ductus arteriosus. / Iwai, Kenji; Nagasawa, Kazumichi; Akaike, Toru; Oshima, Toshio; Kato, Takashi; Minamisawa, Susumu.

    In: Biochemical and Biophysical Research Communications, Vol. 503, No. 4, 18.09.2018, p. 3242-3247.

    Research output: Contribution to journalArticle

    Iwai, Kenji ; Nagasawa, Kazumichi ; Akaike, Toru ; Oshima, Toshio ; Kato, Takashi ; Minamisawa, Susumu. / CCN3 secreted by prostaglandin E2 inhibits intimal cushion formation in the rat ductus arteriosus. In: Biochemical and Biophysical Research Communications. 2018 ; Vol. 503, No. 4. pp. 3242-3247.
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