This series showcases video summaries of new findings published in the Journal of Clinical Investigation. This format allows authors to to provide a personally guided tour of their results and makes the research more accessible to a broad readership. The JCI accepts videos from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
β cell dysfunction is a hallmark of type 2 diabetes (T2D) and is associated with extracellular accumulation of amyloid plaques comprised of islet amyloid polypeptide (IAPP). Human IAPP is potentially toxic and has been shown to accumulate within β cells of T2D patients and in transgenic rodent models. In this episode, Safia Costes and colleagues examine the role of autophagy in the degradation of human IAPP in murine models. Human IAPP aggregated within p62-positive inclusions in transgenic animals, with no apparent loss of β cell function or mass; however, human IAPP-expressing mice with a β cell-specific autophagy defect developed overt diabetes due β cell death. These results indicate that autophagy is protective against IAPP-induced toxicity in β cells and suggest the autophagy pathway as a potential theraputic target for treatment and/or prevention of T2D.
In virto fertilization (IVF) has helped millions of couples have children. While considered relatively safe, there are risks associated with this procedure. Among the more serious complications is the development of ovarian hyperstimulation syndrome (OHSS), which in extreme cases can be fatal. OHSS results from excessive stimulation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG), which is commonly used as part of the IVF cycle to promote egg maturation. In this episode, Waljit Dhillo discusses the results from a small clinical trial that evaluated use of the fertility hormone kisspeptin-54 for egg maturation in IVF. Dhillo and colleagues report that kisspeptin-54 treatment resulted in mature eggs that were successfully fertilized and transferred, with pregnancy in 23% of patients.
Fibrosis is a hallmark of chronic kidney disease that is characterized by accumulation of extracellular matrix and an influx of immune cells. Autophosphorylation of serine residues within the type II TGF-β receptor (TβRII) following activation by TGF-β induces a SMAD-dependent profibrotic signaling cascade; however, there are multiple tyrosine residues within the cytoplasmic tail of TβRII that have potential to regulate this pathway. In this episode, Ambra Pozzi reveals that phosphorylation of tyrosine residues in the cytoplasmic tail of TβRII does influence the fibrotic signaling cascade. Specifically, Pozzi and colleagues determined that integrin α1β1 recruits the phosphatase TCPTP to TβRII, subsequently dephosphorylating tyrosine residues within the TβRII cytoplasmic tail. Furthermore, mice lacking α1β1 integrin exhibited enhanced phosphorylation of TβRII due to decreased recruitment of TCPTP, resulting in severe fibrosis following kidney injury.
Pulmonary hypertension is a complex disease that affects multiple vascular cell types, and mircoRNAs (miRNAs) have been implicated in the pathogenesis of this condition. In this episode, Stephen Chan discusses how his group used network theory to identify miRNA-130/301 as a regulator of a system of miRNAs that promote the development of pulmonary hypertension. Furthermore, inhibition of miR130/301 prevented the development on pulmonary hypertension in a hypoxic murine model. The results of this study support the use of network analysis for identifying complex miRNA-regulated pathways involved in disease manifestations.
The maternal environment not only affects in utero development, but also can dramatically influence postnatal phenotypes. In this episode, Vijay Yadav, Isabel Quiros-Gonzalez, and Liesbet Lieben discuss their use of a murine genetic model to evaluate the effects of maternal vitamin B12 deficiency on offspring bone formation. Pups from B12-deficient mothers exhibited growth retardation and reduced bone mass due to a loss of taurine synthesis in the liver. Furthermore, administration of taurine to these offspring enhanced bone formation, ameliorating growth defects. The results from this study suggest that B12/taurine supplementation may be a potential therapeutic strategy to increase bone mass.
Copyright © 2014 American Society for Clinical Investigation