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PUBLIC RELEASE DATE:
5-Jun-2008

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Contact: Karen Honey
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Journal of Clinical Investigation
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JCI online early table of contents: June 5, 2008

EDITOR'S PICK: Finding the source: cells that initiate a common infant tumor identified

Infantile hemangiomas, exemplified by the strawberry-like patches that appear on the skin of infants soon after birth, are benign tumors that develop in 5%-10% of Caucasian infants and usually disappear by the age of 9 without treatment. Joyce Bischoff and colleagues, at Children's Hospital Boston, have now identified the cells that give rise to these tumors and used them to develop a new mouse model of this disease.

Cells expressing the protein CD133 were isolated from infantile hemangioma tissue and individual cells were grown separately in culture. After each cell had been grown long enough for it to have given rise to a large population of cells, the cells were transplanted into immunodeficient mice, where they generated human blood vessels. Overtime, the number of blood vessels decreased and fat cells became evident. As these observations recapitulate those made in individuals with infantile hemangioma -- where blood vessels form and then disappear leaving behind fat cells -- the authors conclude that a single cell can give rise to infantile hemangioma and that their new model of these tumors will help identify therapeutic targets.

TITLE: Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice

AUTHOR CONTACT:
Joyce Bischoff
Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 919-2192; Fax: (617) 730-0231; E-mail: joyce.bischoff@childrens.harvard.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33493


GASTROENTEROLOGY: The protein IRF4 takes control of inflammation in the gut

Individuals with inflammatory bowel diseases (IBDs) experience episodes of inflammation in their gut that can cause abdominal pain, vomiting, and diarrhea, among other things. Exactly what causes IBD has not been determined but it is now considered to involve inappropriate over activation of the immune system in the gut, and the proinflammatory factor IL-6 is thought to have a crucial role in this. New insight into the molecular mechanisms controlling IL-6 production in a mouse model of IBDs has now been provided by Markus Neurath and colleagues, at the University of Mainz, Germany, and might lead to the development of new drugs to treat individuals with IBDs.

Initial analysis indicated that a molecule known as IRF4, which regulates several functions in immune cells known as T cells, was expressed at higher levels in T cells in the gut of individuals with IBDs than in the gut of healthy individuals. Consistent with increased IRF4 having an important role in the development of IBD, T cells from mice lacking IRF4 did not cause intestinal inflammation when transplanted into immunodeficient mice, whereas normal T cells did. Further, IRF4-deficient mice were protected from intestinal inflammation in two other models of IBD, and this protection was overcome by the administration of IL-6 to the mice. The authors therefore conclude that IRF4 is a crucial regulator of IL-6 production in the intestine and that targeting IRF4 might provide a new approach to treating individuals with IBDs.

TITLE: The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6

AUTHOR CONTACT:
Markus F. Neurath
University of Mainz, Mainz, Germany.
Phone: 49-6131-175740; Fax: 49-6131-175583; E-mail: neurath@1-med.klinik.uni-mainz.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33227


NEUROBIOLOGY: Improving brain function in rats following a stroke

A team of researchers from Academia Sinica, Taipei, Republic of China, and China Medical University Hospital, Taichung, Republic of China, have now shown that rats transplanted with cells isolated from human nasal polyps have improved brain function following a stroke compared with rats not transplanted with these cells. The authors therefore suggest that isolating these cells from individuals who have had a stroke and transplanting them back into the brains of these individuals might provide clinical benefit.

In the study, cells known as olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) were isolated from human nasal polyps and characterized in vitro. Rats implanted with human OECs and ONFs performed better in tasks measuring their brain function (e.g., tasks assessing their movement) following a stroke than did rats not transplanted with these cells. Further work determined some of the mechanisms by which OECs and ONFs mediated their beneficial effects. Specifically, OECs and ONFs induced nerve cell growth by a process that involved increased expression of the soluble factor SDF-1-alpha, the protein to which it binds, and cellular prion protein. In addition, when transplanted into mice, OECs and ONFs induced stem cells to home to the site of brain damage following a stroke.

TITLE: Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke

AUTHOR CONTACT:

Hung Li
Institute of Molecular Biology, Academia Sinica, Taipei, Republic of China.
Phone: 886-2-2788-0460; Fax: 886-2-2782-6085; E-mail: hungli@ccvax.sinica.edu.tw.

Demeral David Liu
China Medical University Hospital, Taichung, Republic of China.
Phone: 886-4-22052121 ext. 6034; Fax: 886-4-22080666; E-mail: liudm@mail.ndmctsgh.edu.tw.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34363


NEPHROLOGY: New molecular link between diabetes and kidney failure

Diabetes is an increasingly common cause of kidney failure in developed countries. It is thought that activation of a hormone system known as the renin-angiotensin system (RAS) early in the course of diabetes has an important role in the development of kidney disease. New data, generated using mice, rats, and rabbits, by János Peti-Peterdi and colleagues, at the University of Southern California, Los Angeles, have provided new insight into the mechanisms by which the RAS might be activated in individuals with diabetes.

Individuals with diabetes have increased levels of glucose in their blood and other bodily fluids. In the study, in vitro exposure of rat, mouse, and rabbit kidney to high levels of glucose triggered cells in the kidney to release renin and this was associated with accumulation of a molecule known as succinate. Consistent with this having a role in human diabetes, diabetic mice had higher levels of succinate in their kidney than did nondiabetic mice. Furthermore, diabetic mice lacking the protein GPR91, which recognizes succinate, had less renin in their kidney that did diabetic mice expressing GPR91. The authors therefore suggest that GPR91 might be a new therapeutic target to prevent the kidney failure that can be a complication of diabetes.

TITLE: Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney

AUTHOR CONTACT:
János Peti-Peterdi
University of Southern California, Los Angeles, California, USA.
Phone: (323) 442-4337; Fax: (323) 442-4466; E-mail: petopete@usc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33293


INFLAMMATION: Why alcohol is bad for your pancreas

Much is known about the mechanisms by which excessive alcohol consumption causes damage to organs such as the liver, heart, and brain. However, only recently has progress been made in understanding how excessive alcohol consumption causes damage to the pancreas, and new insight into the molecular mechanisms underlying pancreatic damage in mice following alcohol exposure has now been provided by Herbert Gaisano and colleagues at the University of Toronto and University Health Network, Canada.

Rodents who have been fed alcohol in their diet and then exposed to a drug known as carbachol develop an inflammation of the pancreas (pancreatitis) that resembles the pancreatitis seen in individuals who consume an excessive amount of alcohol. It has been suggested previously that the rodents develop pancreatitis because the alcohol and carbachol exposure cause cells in the pancreas to release vesicles containing degradative proteins known as enzymes at inappropriate places. In the study, a protein known as VAMP8 was found to have an important role in coordinating the inappropriate release of enzyme-containing vesicles in mice exposed to alcohol and carbachol. As such, mice lacking VAMP8 showed reduced pancreatitis after exposure to alcohol and carbachol.

TITLE: VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis

AUTHOR CONTACT:
Herbert Y. Gaisano
University of Toronto, Toronto, Ontario, Canada.
Phone: (416) 978-1526; Fax: (416) 978-8765; E-mail: herbert.gaisano@utoronto.ca.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34672


PHYSIOLOGY: The protein Hip1r soothes the stomach

New data, generated in mice, by Linda Samuelson and colleagues, at the University of Michigan, Ann Arbor, have defined a new role for the protein Hip1r in ensuring that cells in the lining of the stomach that are known as parietal cells function normally.

One of the main functions of parietal cells is to secrete acid, which is stored inside special compartments in the cell known as vesicles, into the stomach to promote the digestion of food. As Hip1r was found to be required for parietal cells to transport their acid-containing vesicles to the surface where the acid is released, mice lacking Hip1r had less acid in their stomach. In addition, the defect in acid-containing vesicle transport caused many of the parietal cells to die by a process known as apoptosis. These effects were associated with other changes in the lining of the stomach that resembled changes seen in the human stomach lining in the progression to stomach cancer. The authors therefore conclude that Hip1r has an important role in maintaining normal stomach function.

TITLE: Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

AUTHOR CONTACT:
Linda C. Samuelson
The University of Michigan, Ann Arbor, Michigan, USA.
Phone: (734) 764-9448; Fax: (734) 763-1166; E-mail: lcsam@umich.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33569

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