Author's Take
In this video collection, authors of findings published in JCI Insight present personally guided tours of their results. The journal accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive pulmonary fibrosis and eventual loss of function. The transcription factor Wilms’ tumor 1 (WT1) promotes cell proliferation and is critical for lung development. This factor has been shown to be upregulated in IPF; however, the role of WT1 in IPF development is not fully understood. In this episode, Satish Madala and colleagues used lineage tracing to show that WT1 promotes fibroblast activation, fibroproliferation, myofibroblast transformation, and ECM production in a murine model of IPF. Moreover, partial loss of WT1 reduced fibrotic phenotypes. Together, these results identify WT1 as an important driver of lung fibrosis and support further exploration of WT1 as a therapeutic target.
White adipose tissue (WAT) serves primarily as energy storage; however, in response to cold or β-adrenergic agonists, WAT develops characteristics of brown adipose tissue (BAT), which expends energy in the form of heat. WAT beiging has proposed as potential strategy for treating obesity. In this episode, Philip Kern and colleagues exposed lean and obese subjects to cold or treatment with the β3 agonist mirabegron and evaluated markers of adipose beiging. Both treatments induced beiging, regardless of obesity status or age. The results of this study support further evaluation of the long-term effects of induced adipose beiging for treatment of obesity and associated metabolic dysfunction.
Spontaneous mutations in the gene encoding the tumor suppressor p53 (TP53) are frequently identified in human cancers and most of these mutations are the result of missense substitutions, which can result in complete loss of p53 function or retention of some activity. In this episode, Jean Gariépy and Nicholas Fischer discuss their work, which reveals that the level of residual transcriptional activity of mutant p53 associates with improved survival in males with glioma and gastric adenocarcinoma. This association was sex-specific, as similar links were not observed in females with p53-mutant cancers. Moreover, evaluation of patients with Li-Fraumeni syndrome (LFS), which results from germline mutations in TP53 revealed a link between residual p53 activity and prolong lifetime cancer survival. Together, these results support p53 transcriptional activity as a prognostic factor for men with glioma and gastric adenocarcinoma.
Several different factors, including alcohol use and hepatitis C virus (HCV) infection, underlie chronic liver disease. Regardless of the cause, chronic liver disease progress in a similar fashion, ultimately resulting in hepatic fibrosis and loss of organ function. In this episode, Matthew Sweet and colleagues performed gene expression profiling on liver biopsies from patients at different stages of fibrosis with varying disease etiologies. Using this approach, the authors identified genes associated with advanced fibrosis and demonstrated that levels of at least one of the gene products, VCAN, is elevated in serum from patients with advanced fibrosis. Additionally, a set of steatosis-associated genes and serum markers was identified in an HCV patient cohort and validated in a murine model. These common gene signatures have potential as both biomarkers and therapeutic targets of chronic liver disease.
Fetal growth restriction during pregnancy can lead to a variety of complications, including still birth and increased risk of cardiovascular and metabolic disease later in life. Placental volume can be used to predict adverse regency outcomes, including risk of an infant being small for gestational age; however, determination of placental volume is time consuming, requiring an operator to manually identify and annotate the placenta. In this episode, Sally Collins and Pádraig Looney describe the development of a technique that allows for automated segmentation of the placenta and volume determination from 3D ultrasound images. This technique has potential for wide-spread use for predicting small gestational age.
