Hypoxia-inducible factor-3α promotes angiogenic activity of pulmonary endothelial cells by repressing the expression of the VE-cadherin gene.

The variants of the hypoxia-inducible factor-3α gene HIF-3α and NEPAS are known to repress the transcriptional activities driven by HIF-1α and HIF-2α. Although NEPAS has been shown to play an important role in vascular remodeling during lung development, little is known about the roles of HIF-3α in adult lung function. Here, we examined pulmonary endothelial cells (ECs) isolated from wild-type (WT) and HIF-3α functional knockout (KO) mice. The expression levels of angiogenic factors (Flk1, Ang2 and Tie2) were significantly greater in the HIF-3α KO ECs than those in the WT ECs irrespective of oxygen tension. However, the HIF-3α KO ECs showed impaired proliferative and angiogenic activities. The impaired EC function was likely due to the excess vascular endothelial (VE)-cadherin, an inhibitor of Flk1/PI3 kinase/Akt signaling, as treatment of the cells to a neutralizing antibody partly restored the phenotype of the HIF-3α KO ECs. Importantly, we found that the mRNA levels of HIF-2α and Ets-1 were significantly increased by HIF-3α ablation. Given that both factors are known to activate the VE-cadherin gene, the transcriptional repression of these factors by HIF-3α might be important for silencing the irrelevant expression of the VE-cadherin gene. Collectively, these data show novel and unique roles of HIF-3α for angiogenic gene regulation in pulmonary ECs.

AtSAP130/AtSF3b-3 function is required for reproduction in Arabidopsis thaliana.

Flowering plants produce multicellular gametophytes through an elaborate regulation of gametogenesis. During female and male gametogenesis in Arabidopsis thaliana, sporogenous cells differentiate and undergo meiosis to produce megaspores and microspores, which in turn go through mitosis to develop into multicellular gametophytes. Here we report that the Arabidopsis spliceosomal protein, SPLICEOSOME-ASSOCIATED PROTEIN 130 (AtSAP130), is required for proper reproduction. AtSAP130 is encoded by two genes, AtSAP130a and AtSAP130b. Plants with reduced expression of the AtSAP130 genes, induced by RNA interference, showed a defect in fertilization. Besides functional impairment observed in the female reproductive organs, analysis focusing on pollen development revealed defects in the transition from the microspore to the bicellular stage. Our results suggest that AtSAP130a and AtSAP130b play an indispensable role in specific spatiotemporal events in reproduction.