JCI online early table of contents: Oct. 1, 2010

Growth hormone is used to treat children's growth disorders and has been used by some sports men and women to promote muscle growth and regeneration. This is because it coordinates skeletal muscle development, nutrient uptake, and nutrient utilization. It is not clear, however, which of these effects are direct and which are indirectly mediated via growth hormone induction of the protein IGF-1. Now, however, a team of researchers, led by Thomas Clemens, at Johns Hopkins University School of Medicine, Baltimore, has used mice engineered to lack in their skeletal muscle either the molecule to which growth hormone binds or the molecule to which IGF-1 binds to show that growth hormone control of skeletal muscle development is dependent on IGF-1, whereas its control of nutrient uptake is independent of IGF-1. The authors hope that with additional work, these results will guide more informed use of growth hormone or growth hormone analogs for promoting muscle development and reducing muscle loss.

TITLE: Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

AUTHOR CONTACT:
Thomas L. Clemens
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Phone: 410.955.3245; Fax: 410.614.1451; E-mail: tclemen5@jhmi.edu.

View this article at: http://www.jci.org/articles/view/42447?key=0f67533b542cb2ccea78

CARDIOVASCULAR DISEASE: How the drugs work to reduce mortality in blood vessel disease

Drugs that antagonize the hormone aldosterone have been shown in clinical trails to reduce mortality in individuals with atherosclerosis — a disease sometimes known as hardening of the arteries that is a major cause of heart attack and stroke. Aldosterone increases blood pressure via effects on the protein MR, but the beneficial effects of aldosterone antagonists in individuals with atherosclerosis far outweighed their modest effect on blood pressure. It has therefore been suggested that aldosterone has more direct atherosclerosis-promoting effects. One such effect has now been uncovered by a team of researchers led by Iris Jaffe, at Tufts Medical Center, Boston. Specifically, the team found that aldosterone, via effects on MR, induces expression of the protein PGF in mouse and human blood vessel walls and that PGF augments blood vessel injury. The team therefore suggest that targeting the blood vessel aldosterone/MR/PGF pathway might provide a new approach to reducing mortality in individuals with atherosclerosis.

TITLE: Placental growth factor mediates aldosterone-dependent vascular injury in mice

AUTHOR CONTACT:
Iris Z. Jaffe
Tufts Medical Center, Boston, Massachusetts, USA.
Phone: 617.636.0620; Fax: 617.636.1444; E-mail: ijaffe@tuftsmedicalcenter.org.

View this article at: http://www.jci.org/articles/view/40205?key=a2a49a72faba7a68a1e8

Chronic kidney disease (the slow loss of kidney function over time) is a major healthcare burden. In the United States, it is estimated that more than 20 million adults have significantly reduced kidney function. New research, in mice and humans, led by Fabiola Terzi, at INSERM U845, Hôpital Necker Enfants Malades, France, has now identified the protein lipocalin 2 as a player in progression of chronic kidney disease to end-stage kidney failure, a condition requiring dialysis or transplantation. As lipocalin 2 levels were found to be increased particularly in patients who rapidly progressed to end-stage kidney failure, the authors suggest that it is worth studying in large patient cohorts whether lipocalin 2 is a good biomarker of progression of chronic kidney disease to end-stage kidney failure. Identifying such individuals might allow clinicians to intervene more aggressively and postpone kidney failure.

TITLE: Lipocalin 2 is essential for chronic kidney disease progression in mice and humans

AUTHOR CONTACT:
Fabiola Terzi
INSERM U845, Université Paris Descartes, Hôpital Necker Enfants Malades, Paris, France.
Phone: 33.1.44495245; Fax: 33.1.44490290; E-mail: fabiola.terzi@inserm.fr.

View this article at: http://www.jci.org/articles/view/42004?key=59e1b0d3c147af02ca2a

The main cause of death for individuals with the rare genetic disorder Fanconi anemia is depletion of bone marrow cells, which leads to bone marrow failure. Fanconi anemia is caused by mutations in any one of several genes that generate proteins that cooperate in a DNA repair pathway known as the Fanconi anemia pathway. New data, generated by Alan D'Andrea and colleagues, at the Dana-Farber Cancer Institute, Boston, now indicates that the Fanconi anemia pathway is involved in mouse and human bone marrow cell division. They therefore propose that the depletion of bone marrow cells in individuals with Fanconi anemia could be due, at least in part, to a failure of bone marrow cells to divide, a cellular defect associated with apoptotic cell death.

TITLE: Cytokinesis failure occurs in Fanconi anemia pathway–deficient murine and human bone marrow hematopoietic cells

AUTHOR CONTACT:
Alan D. D'Andrea
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Phone: 617.632.2112; Fax: 617.632.5757; E-mail: Alan_dandrea@dfci.harvard.edu.

View this article at: http://www.jci.org/articles/view/43391?key=aa4a36a67cffea2848e0

Type 2 diabetes is usually preceded by resistance to the hormone insulin, which regulates levels of glucose in the blood. Excessive production of glucose by the liver is a key factor in progression to type 2 diabetes in individuals who are resistant to the effects of insulin. Recent in vitro data indicate that the protein MKP-3 can promote the expression of genes involved in the generation of glucose by the liver, but whether this is true in vivo was not assessed. Now, a team of researchers, led by Zhidan Wu, at Novartis Institutes for BioMedical Research, Cambridge, and Haiyan Xu, at Brown Medical School, Providence, has shown in mice that MKP-3 promotes the production of glucose by the liver in vivo. The team therefore suggests that MKP-3 might provide a new therapeutic target for the treatment of obesity-related type 2 diabetes.

TITLE: MAPK phosphatase𔃁 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice

AUTHOR CONTACT:

Zhidan Wu
Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
Phone: 617.871.7345; Fax: 617.871.7051; E-mail: zhidan.wu@novartis.com.

Haiyan Xu
Brown Medical School, Providence, Rhode Island, USA.
Phone: 401.444.0347; Fax: 401.444.3784; E-mail: hxu@lifespan.org.

View this article at: http://www.jci.org/articles/view/43250?key=b09a353e33c31db24501

CD8+ T cells are key mediators of the immune response against viruses that invade our body. The fate of these cells after the initial antiviral response varies depending on the identity of the virus and on whether the virus is cleared from the body or persists. In the case of persistent human cytomegalovirus (HCMV) infection, a large number of virus-specific, quiescent, effector-type CD8+ T cells with constitutive killing activity remain after the initial immune response. New research, using HCMV-specific CD8+ T cells collected from patients infected with HCMV, led by René van Lier, at the Academic Medical Center, Amsterdam, the Netherlands, now suggests that the enduring effector cell properties of these cells are important in preventing reactivation of persistent HCMV.

TITLE: Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation

AUTHOR CONTACT:
René A.W van Lier
Academic Medical Center, Amsterdam, the Netherlands.
Phone: 31.20.566.6303; Fax: 31.20.566.9756; E-mail: r.vanlier@amc.nl.

View this article at: http://www.jci.org/articles/view/42758?key=13f45beb5c32bb01cec3