Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus
Autor: | Junichi Saito, Kazuo Seki, Shigeru Nishimaki, Shuichi Ito, Azusa Uozumi, Utako Yokoyama, Satoko Ito, Yoshihiro Ishikawa, Takahiro Kemmotsu, Shiho Iwasaki |
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Rok vydání: | 2019 |
Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Myocytes Smooth Muscle 030204 cardiovascular system & hematology Betamethasone 03 medical and health sciences 0302 clinical medicine Cell Movement Pregnancy Ductus arteriosus Internal medicine Animals Medicine cardiovascular diseases 030212 general & internal medicine ADP Ribose Transferases Respiratory distress business.industry Ductus Arteriosus General Medicine Rats medicine.anatomical_structure embryonic structures cardiovascular system Cardiology Female Thickening Tunica Intima Cardiology and Cardiovascular Medicine business Standard therapy Glucocorticoid medicine.drug |
Zdroj: | Circulation Journal. 83:654-661 |
ISSN: | 1347-4820 1346-9843 |
Popis: | Antenatal betamethasone (BMZ) is a standard therapy for reducing respiratory distress syndrome in preterm infants. Recently, some reports have indicated that BMZ promotes ductus arteriosus (DA) closure. DA closure requires morphological remodeling; that is, intimal thickening (IT) formation; however, the role of BMZ in IT formation has not yet been reported. Methods and Results: First, DNA microarray analysis using smooth muscle cells (SMCs) of rat preterm DA on gestational day 20 (pDASMCs) stimulated with BMZ was performed. Among 58,717 probe sets, ADP-ribosyltransferase 3 (Art3) was markedly increased by BMZ stimulation. Quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed the BMZ-induced increase of Art3 in pDASMCs, but not in aortic SMCs. Immunocytochemistry showed that BMZ stimulation increased lamellipodia formation. BMZ significantly increased total paxillin protein expression and the ratio of phosphorylated to total paxillin. A scratch assay demonstrated that BMZ stimulation promoted pDASMC migration, which was attenuated byArt3-targeted siRNAs transfection. pDASMC proliferation was not promoted by BMZ, which was analyzed by a 5'-bromo-2'-deoxyuridine (BrdU) assay. Whether BMZ increased IT formation in vivo was examined. BMZ or saline was administered intravenously to maternal rats on gestational days 18 and 19, and DA tissues were obtained on gestational day 20. The ratio of IT to tunica media was significantly higher in the BMZ-treated group.These data suggest that antenatal BMZ administration promotes DA IT through Art3-mediated DASMC migration. |
Databáze: | OpenAIRE |
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