News From The Journal Of Clinical Investigation, June 1, 2009

Main Category: Immune System / Vaccines
Also Included In: Respiratory / Asthma;  Vascular;  Diabetes
Article Date: 02 Jun 2009 - 5:00 PDT

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IMMUNOLOGY: Chronic prostatitis is an autoimmune condition

Chronic prostatitis/chronic pelvic pain syndrome is a common disease that causes pelvic pain in men. The cause of chronic prostatitis is unknown and there are no specific treatments for the condition. However, insight into the cause of chronic prostatitis has now been provided by Lawrence Fong and colleagues, at UCSF, San Francisco, who have determined that it is an autoimmune disease.

In this study, the researchers initially analyzed mice lacking the protein Aire because they develop spontaneous prostatitis. These mice were found to mount an immune response, mediated by cells known as B and T cells, that was directed toward the prostate protein SVS2. The importance of this immune response was highlighted by the observation that normal mice injected with SVS2 developed prostatitis. Of clinical relevance, immune molecules (specifically antibodies) that target the human SVS2-like seminal vesicle protein semenogelin were detected in patients with chronic prostatitis. The authors hope that defining chronic prostatitis as an autoimmune disease and semenogelin as the target of the immune system might provide new approaches to the diagnosis and treatment of the condition.

TITLE: An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans
AUTHOR CONTACT:
Lawrence Fong
University of California, at San Francisco, San Francisco, California, USA.
https://www.the-jci.org/article.php?id=38332

PULMONARY: New pathway underlying pulmonary hypertension

Pulmonary hypertension is an unremitting disease caused by a progressive increase in blood pressure in the blood vessels of the lung; it leads to heart failure and ultimately death. Currently there are limited treatment options. However, You-Yang Zhao and colleagues, at the University of Illinois College of Medicine, Chicago, have identified in mice a new molecular pathway underlying pulmonary hypertension that they hope might provide novel therapeutic targets.

In the study, mice lacking either caveolin 1, eNOS, or both proteins were used to determine that chronic eNOS activation, secondary to loss of caveolin-1, can lead to pulmonary hypertension. Further analysis revealed that the chronic eNOS activation that induced pulmonary hypertension was associated with impaired activity of the protein PKG because it was modified by a process known as nitration. As lung tissue from patients with a form of pulmonary hypertension known as idiopathic pulmonary arterial hypertension exhibited evidence of increased eNOS activation and PKG nitration and reduced caveolin-1 expression, the authors suggest that preventing and/or reversing PKG nitration might be of benefit to individuals with idiopathic pulmonary arterial hypertension.

TITLE: Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration
AUTHOR CONTACT:
You-Yang Zhao
University of Illinois College of Medicine, Chicago, Illinois, USA.
https://www.the-jci.org/article.php?id=33338

VASCULAR BIOLOGY: New function for the peptides ANP and BNP

Michaela Kuhn and colleagues, at the University of Würzburg, Germany, have identified in mice a new function for the molecules ANP and BNP: they help coordinate the formation of new blood vessels following tissue stress.

In the heart, ANP and BNP have a role in regulating blood pressure and volume. In the study, the researchers analyzed mice lacking the molecule to which ANP and BNP bind (GC-A) in every cell, in endothelial cells, or in smooth muscle cells. The formation of new blood vessels in a hind leg muscle stressed after its blood supply was experimentally restricted was severely impaired in both mice lacking GC-A in all cells and mice lacking GC-A in endothelial cells, but it was normal in mice lacking GC-A in smooth muscle cells. A similar reduction in the formation of new blood vessels was observed in the heart of mice lacking GC-A in endothelial cells after being exposed to the stress of high blood pressure. As BNP expression was increased in hind leg muscle and heart muscle under these stress conditions, the authors suggest that BNP acts on endothelial cells to regulate blood vessel formation.

TITLE: The natriuretic peptide/guanylyl cyclase-A system functions as a stress-responsive regulator of angiogenesis in mice
AUTHOR CONTACT:
Michaela Kuhn
Physiologisches Institut der Universität Würzburg, Würzburg, Germany.
https://www.the-jci.org/article.php?id=37430

METABOLIC DISEASE: Developing insulin-producing cells

Underlying the progression of both type 1 and type 2 diabetes is decreased levels of the hormone insulin. This insulin defect is due to decreased numbers of beta-cells in the pancreas, suggesting that beta-cell replacement therapies might be of clinical benefit. Understanding how beta-cells develop is of prime importance for developing such approaches. New insight into this has now been provided by Doris Stoffers and colleagues, at the University of Pennsylvania School of Medicine, Philadelphia, who have discerned the molecular mechanism by which the protein Pdx1 governs early embryonic development of the mouse pancreas. The information obtained from this study is likely to help determine the requirements for manipulating multipotent cells to generate insulin-producing beta-cells. In addition, these data suggest a mechanism to explain why mutations in one of an individual's two copies of the PDX1 gene are associated with both type 2 diabetes and an inherited form of diabetes known as MODY4.

TITLE: The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice http://www.eurekalert.org/pub_releases/2009-06/stoffers@mail.med.upenn.edu
AUTHOR CONTACT:
Doris A. Stoffers
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Source:
Karen Honey
Journal of Clinical Investigation