Articles in 2012

Vascular homeostasis in the lung is disturbed in pulmonary arterial hypertension. Jongmin Kim et al. delineate a new signaling axis controlling endothelial cell proliferation and cytokine production that is dysregulated in pulmonary endothelial cells from individuals with this disease. In this axis, the peptide apelin controls expression of the cytokine FGF2, a mitogen for endothelial and vascular smooth-muscle cells, through effects on two microRNAs. The authors also demonstrated the functional importance of these miRNAs in rat models of pulmonary hypertension.

The early events in the pathogenesis of type 1 diabetes remain incompletely understood. Julien Diana et al. now show that in response to physiological beta cell death, innate immune cells including neutrophils and B1-a cells are recruited early on to pancreatic islets. These cells promote interferon-α production by plasmacytoid dendritic cells in the pancreas, promoting autoreactive T cell responses and autoimmunity.

The glomerulus, unlike many capillary beds, readily supports leukocyte recruitment, but little is known about the actions of leukocytes upon recruitment to glomeruli. Devi and colleagues have addressed this issue with a multiphoton, confocal microscopy–based approach to shed light on glomerular inflammation. Induction of inflammation in mice did not increase the number of leukocytes recruited to glomeruli but prolonged the duration of leukocyte retention and migration.

Whether the molecular drivers of tumor initiation are the same factors that promote metastasis during tumor progression is addressed in this report. In renal carcinoma, common primary driving alterations such as VHL loss do not necessarily correlate with outcome, and the authors show that additional epigenetic adaptations are required to unleash prometastatic behavior. Two important metastastic drivers, CXCR4 and CYTIP, are activated downstream of VHL loss through epigenetic reprogramming involving differential chromatin modification or DNA methylation, exemplifying the complex evolution of tumorigenic traits downstream of driving alterations.

In a new study Yingxian Li and her colleagues show that the microRNA miR-214 targets ATF4 in osteoblasts to negatively regulate their activity. Manipulating miR-214 levels experimentally showed that its elevated expression is sufficient to induce bone loss in mice and that its therapeutic inhibition reduces bone loss in two mouse models.

A year ago, Guido Rasi stepped into the role of executive director of the European Medicines Agency (EMA), becoming only the third person to fill that role since the inception of the continental drug advisory body, in 1995. He spoke with Roxanne Khamsi about how the EMA is working toward better safety guidance and improved transparency.

We list the key people who made headlines this year, either for public reports that overstretched their reach or for papers that almost never saw the light of day.