Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus.

BACKGROUND: 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. CONCLUSIONS: These data suggest that antenatal BMZ administration promotes DA IT through Art3-mediated DASMC migration.

ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways.

Triple-negative breast cancers (TNBCs) are defined by lack of expressions of estrogen, progesterone, and ERBB2 receptors. Because biology of TNBC is poorly understood, no targeted therapy has been developed for this breast cancer subtype and chemotherapy is its only systemic treatment modality. In this study, we firstly determined that the expression of human ecto-ADP-ribosyltransferase 3 (ART3) is significantly associated with the basal-like breast cancer subgroup, which is largely overlapped with TNBC, through analyzing published data sets. We also found that ART3 protein is significantly overexpressed in human TNBC tumors tissue and cell lines through using immunohistochemistry and immunoblotting. Overexpression of ART3 in MDA-MB-231 breast cancer cells increased cell proliferation, invasion, and survival in vitro and growth of xenograft tumors. Conversely, knockdown of ART3 in breast cancer cells inhibited cell proliferation and invasion. In addition, we showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance.

Association of polymorphisms in ART3 gene with male infertility in the Chinese population.

The ADP-ribosyltransferase 3 gene (ART3) has been reported to be associated with non-obstructive azoospermia (NOA) in the Japanese population. In this study, we aim to explore the possible association between the four single nucleotide polymorphisms (SNPs) (rs11097230, rs17001385, rs14773 and rs6836703) in ART3 gene and male infertility with spermatogenesis impairment in the Chinese population. The study population included 321 idiopathic infertile males with azoospermia or oligozoospermia and 250 fertile males. Four SNPs of ART3 gene were genotyped using the method of SNaPshot. The results showed that an SNP (rs6836703) in the intron11 region of ART3 gene is significantly associated with male infertility (odds ratio: 0.632, 95% confidence interval: 0.440-0.910). No significant associations were found between any of the other three variants (rs11097230, rs17001385 and rs14773) in ART3 gene and male infertility. SNP rs6836703 in ART3 gene may contribute to male infertility risk in the Chinese population.