EDITOR'S PICK: The protein modifier SUMO helps set apart females and males
One way in which men and women differ is in their expression of liver proteins that control a large number of whole-body processes such as energy generation and lipid and steroid hormone production and turnover. Now, Walter Wahli and colleagues, at the University of Lausanne, Switzerland, have identified a new mechanism underlying this differential expression of proteins in male and female mice.
The protein PPAR-alpha is able to enter the nucleus, where it acts to control the expression of a large number of genes. In the study, PPAR-alpha was found to repress the expression of many liver genes responsible for making proteins involved in immunity and steroid production and turnover only in female mice. One of the genes most strongly repressed in female mice by PPAR-alpha was Cyp7b1, which generates a protein involved in drug breakdown and the generation of cholesterol, steroids, and other fats. Detailed analysis revealed the mechanism by which PPAR-alpha repressed Cyp7b1 expression, it was modified by a process known as sumoylation. Importantly, this only occurred in female mice. As PPAR-alpha–mediated repression protected female mice from estrogen-induced intrahepatic cholestasis, the most common liver disease during pregnancy, the authors suggest that PPAR-alpha agonists might provide a new approach to prevent this disease.
TITLE: Sumoylated PPAR-alpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice
AUTHOR CONTACT:
Walter Wahli
University of Lausanne, Lausanne, Switzerland.
Phone: 41-0-21-692-41-10; Fax: 41-0-21-692-41-15; E-mail: walter.wahli@unil.ch.
View the PDF of this article at: https://www.the-jci.org/article.php?id=39019
EDITOR'S PICK: Circulating tumor cells a MUST WATCH
As the presence of tumor cells circulating in the blood is associated with shortened survival, a method to detect circulating tumor cells could help clinicians hoping to predict a patient's chances of survival and/or monitor a patient's response to treatment. Now, Toshiyoshi Fujiwara and colleagues, at Okayama University Hospital, Japan, have developed a simple imaging system able to do just that. Specifically, they developed an approach to visualize live tumor cells circulating in the peripheral blood of humans and found that the number of live circulating tumor cells reflected the tumor burden, as they decreased in number upon complete surgical removal of primary tumors. The authors therefore hope that their technology will prove to be of immense clinical benefit.
TITLE: A simple biological imaging system for detecting viable human circulating tumor cells
AUTHOR CONTACT:
Toshiyoshi Fujiwara
Okayama University Hospital, Okayama, Japan.
Phone: 81-86-235-7997; Fax: 81-86-235-7884; E-mail: toshi_f@md.okayama-u.ac.jp.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38609
EDITOR'S PICK: New mouse model of a severe kidney disease leads to potential new therapy
X-linked nephrogenic diabetes insipidus (XNDI) is a severe congenital kidney disease caused by mutations in the V2R gene. Currently, there is no effective drug to specifically treat XNDI, mainly because there are no good animal models of the disease. However, Jürgen Wess and colleagues, at the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, have now developed a viable mouse model of XNDI that recapitulates the major manifestations of the human disease. As analysis of the mouse model indicated that disease was associated with increased expression in the kidney of the protein EP4, the authors tested selective EP4 receptor agonists as potential therapeutics, and found that they alleviated all the symptoms of disease. The authors therefore suggest that selective EP4 receptor agonists could be of benefit to individuals with XNDI and hope that their mouse model can be used to test additional new therapeutic strategies.
TITLE: A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus
AUTHOR CONTACT:
Jürgen Wess
National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Phone: (301) 402-3589; Fax: (301) 480-3447; E-mail: jwess@helix.nih.gov.
View the PDF of this article at: https://www.the-jci.org/article.php?id=39680
IMMUNOLOGY: The protein Sirt1 helps keep immune cells in check
TITLE: The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice
AUTHOR CONTACT:
Deyu Fang
University of Missouri, Columbia, Missouri, USA.
Phone: (573) 882-4593; Fax: (573) 882-4287; E-mail: fangd@health.missouri.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38902
DERMATOLOGY: Spot the difference between benign and malignant skin tumors: harder than you'd think
TITLE: A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans
AUTHOR CONTACT:
G. Paolo Dotto
University of Lausanne, Epalinges, Switzerland.
Phone: 41-21-692-5720; Fax: 41-21-692-5705; E-mail: gian-paolo.dotto@unil.ch.
View the PDF of this article at: https://www.the-jci.org/article.php?id=38543
VASCULAR BIOLOGY: New role for the inhibitor of blood clotting ProS in blood vessel development
TITLE: Lack of Protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis
AUTHOR CONTACT:
Greg Lemke
The Salk Institute, La Jolla, California, USA.
Phone: (858) 453-4100 ext. 1542; Fax: (858) 455-6138; E-mail: lemke@salk.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=39325
NEPHROLOGY: Promoting the survival of cells in the kidney
TITLE: Cyclin I activates Cdk5 and regulates expression of Bcl-2 and Bcl-XL in postmitotic mouse cells
AUTHOR CONTACT:
Stuart J. Shankland
University of Washington, Seattle, Washington, USA.
Phone: (206) 543-2346; Fax: (206) 685-8661; E-mail: stuartjs@u.washington.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=37978
Journal
Journal of Clinical Investigation