Basigin is a highly glycosylated transmembrane protein with two immunoglobulin-like domains. We generated mutant mice lacking the basigin gene (Bsg) by gene targeting. Bsg (-/-) embryos developed normally during preimplantation stages. However, the majority of Bsg (-/-) embryos died around the time of implantation. At this time, basigin mRNA was strongly expressed in the trophectoderm, embryo proper, and uterine endometrium of Bsg (+/+) mice. These results suggest that basigin is involved in intercellular recognition during implantation. Embryos which survived the critical period yielded Bsg (-/-) mutant mice. Half of the mutant mice died before 1 month after birth, due to interstitial pneumonia. The surviving adult mutant mice were small and sterile. Spermatogenesis was arrested in the mutant mice. Most of the spermatocytes in the Bsg (-/-) mouse were arrested and degenerated at the metaphase of the first meiosis, and only a small number differentiated to step 1 spermatids. In the female mutants, the ovaries and genital tract were morphologically normal, and the defect was probably in the capability of implantation of the uterus. In conclusion, basigin is an important cell-surface molecule involved in early embryogenesis and reproduction.

Although the phosphatidylinositol 3-kinase to Akt to mammalian target of rapamycin (PI3K-AktmTOR) pathway promotes survival signaling, inhibitors of PI3K and mTOR induce minimal cell death in PTEN (phosphatase and tensin homolog deleted from chromosome 10 ) mutant glioma. Here, we show that the dual PI3K-mTOR inhibitor PI-103 induces autophagy in a form of glioma that is resistant to therapy. Inhibitors of autophagosome maturation cooperated with PI-103 to induce apoptosis through the mitochondrial pathway, indicating that the cellular self-digestion process of autophagy acted as a survival signal in this setting. Not all inhibitors of mTOR synergized with inhibitors of autophagy. Rapamycin delivered alone induced autophagy, yet cells survived inhibition of autophagosome maturation because of rapamycin-mediated activation of Akt. In contrast, adenosine 5′-triphosphate-competitive inhibitors of mTOR stimulated autophagy more potently than did rapamycin, with inhibition of mTOR complexes 1 and 2 contributing independently to induction of autophagy. We show that combined inhibition of PI3K and mTOR, which activates autophagy without activating Akt, cooperated with inhibition of autophagy to cause glioma cells to undergo apoptosis. Moreover, the PI3K-mTOR inhibitor NVP-BEZ235, which is in clinical use, synergized with the lysosomotropic inhibitor of autophagy, chloroquine,

Background Accumulating evidence shows that microRNA-210 (miR-210) holds great promise to improve angiogenesis for brain tissue repair after cerebral ischemia. However, safe and efficient delivery of miR-210 via intravenous administration is still a challenge. In the past decade, exosomes have emerged as a novel endogenous delivery system. Here, c(RGDyK) peptide is conjugated to exosomes, and they are loaded with cholesterol-modified miR-210 (RGD-exo:miR-210). Results In a transient middle cerebral artery occlusion (MCAO) mouse model, the RGD-exo:miR-210 targets the lesion region of the ischemic brain after intravenous administration, resulting in an increase in miR-210 at the site. Furthermore, RGD-exo:miR-210 are administered once every other day for 14 days, and the expressions of integrin β 3 , vascular endothelial growth factor (VEGF) and CD34 are significantly upregulated. The animal survival rate is also enhanced. Conclusions These results suggest a strategy for the targeted delivery of miR-210 to ischemic brain and provide an angiogenic agent for the treatment of ischemic stroke. Electronic supplementary material The online version of this article (10.1186/s12951-019-0461-7) contains supplementary material, which is available to authorized users.