JCI online early table of contents: April 1, 2008

TITLE: A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy

AUTHOR CONTACT:
Leena Bruckner-Tuderman
University Medical Center Freiburg, Freiburg, Germany.
Phone: 49-671-270-6716; Fax: 49-671-270-6936; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34292

PHYSIOLOGY: The protein Gadd45-beta helps rejuvenate the liver

New data, generated in mice, by Guido Franzoso and colleagues at the University of Chicago, have provided insight into the molecular mechanisms underlying liver regeneration.

In the study, mice lacking the protein Gadd45-beta were found to exhibit decreased liver regeneration after part of their liver was removed, and this was due to decreased proliferation of liver cells and increased programmed cell death. These effects were associated with increased activity of the signaling molecule JNK, and the regenerative capacity of the liver was restored to normal if mice were engineered to lack JNK in addition to Gadd45-beta. Together, these data led the authors to suggest that suppressing the signaling molecule JNK might be beneficial during liver regeneration.

TITLE: Gadd45-beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling

AUTHOR CONTACT:
Guido Franzoso
University of Chicago, Chicago, Illinois, USA.
Phone: (773) 702-4729; Fax: (773) 702-3701; E-mail: . or .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33913

HEMATOLOGY: Every loser wins: loss of protein from platelet surface decreases their ability to aggregate

A crucial step in the formation of a blood clot (also known as a thrombus) is the adhesion of blood cells known as platelets to blood vessel walls. This step is mediated in part by interactions between the protein collagen in blood vessel walls and a protein complex on the surface of platelets comprised of GPVI and FcR-gamma. Although drugs targeting platelets benefit patients with various diseases caused by inappropriate blood clotting, such as heart disease, the safety and efficacy of current treatments are limited. A potential new treatment for such diseases has been suggested by the work of Hiroshi Takayama and colleagues, at The University of Shiga Prefecture, Japan.

It was shown that a mouse antibody that depletes GPVI from the surface of platelets can inhibit collagen-induced human platelet aggregation in vitro. This antibody also led to loss of GPVI on the surface of platelets when it was injected into monkeys. The mechanisms underlying this loss of GPVI were then shown to be cAMP-dependent endocytosis of antibody-bound GPVI. The authors therefore concluded that this approach might provide a new antiplatelet strategy for preventing diseases associated with inappropriate blood clotting.