A paternal protein facilitates sperm RNA delivery to regulate zygotic development.

Sperm contributes essential paternal factors, including the paternal genome, centrosome, and oocyte-activation signals, to sexual reproduction. However, it remains unresolved how sperm contributes its RNA molecules to regulate early embryonic development. Here, we show that the Caenorhabditis elegans paternal protein SPE-11 assembles into granules during meiotic divisions of spermatogenesis and later matures into a perinuclear structure where sperm RNAs localize. We reconstitute an SPE-11 liquid-phase scaffold in vitro and find that SPE-11 condensates incorporate the nematode RNA, which, in turn, promotes SPE-11 phase separation. Loss of SPE-11 does not affect sperm motility or fertilization but causes pleiotropic development defects in early embryos, and spe-11 mutant males reduce mRNA levels of genes crucial for an oocyte-to-embryo transition or embryonic development. These results reveal that SPE-11 undergoes phase separation and associates with sperm RNAs that are delivered to oocytes during fertilization, providing insights into how a paternal protein regulates early embryonic development.

Overexpression of GLP-1 receptors suppresses proliferation and cytokine release by airway smooth muscle cells of patients with chronic obstructive pulmonary disease via activation of ABCA1.

Glucagon-like peptide-1 (GLP­1) is an important insulin secretagogue that possesses anti­inflammatory effects. GLP­1 receptor (GLP­1R) agonists have been demonstrated to serve a pivotal role in the treatment of obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). However, the specific function and underlying mechanisms of GLP­1R in COPD remain uncertain. The aim of the present study was to investigate the action and underlying mechanisms of GLP­1R in airway smooth muscle (ASM) cells from COPD patients. GLP­1R expression levels were markedly decreased in ASM cells from COPD patients compared with those from healthy controls. ASM cell proliferation and migration, and the levels of the inflammatory cytokines interleukin (IL)­1ß, IL­4, tumor necrosis factor (TNF)­α, and granulocyte­macrophage colony­stimulating factor (GM­CSF) were measured. Transfection of pcDNA3.1­GLP­1R had inhibitory effects on ASM cell proliferation and migration, whereas GLP­1R small interfering (si)RNA reversed these effects. Furthermore, the present study demonstrated that GLP­1R overexpression markedly suppressed IL­1ß, IL­4, TNF­α and GM­CSF levels. GLP­1R overexpression upregulated the expression levels of adenosine triphosphate­binding cassette, subfamily A, member 1 (ABCA1) in ASM cells, and the effects of GLP­1R on cell proliferation and migration, and inflammatory cytokine expression in ASM cells was abolished by siRNA­mediated silencing of ABCA1. The results of the present study suggested that GLP­1R contributes to COPD pathology, potentially via an ABCA1­mediated pathway.