March 7, 2008

Aliquots — Research highlights from VUMC laboratories

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We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

New player in gastric cancer

Gastric cancer is the second most common cause of cancer deaths worldwide, and the majority of gastric tumors are resistant to current treatments. To find new therapeutic targets, Wael El-Rifai, M.D., Ph.D., and colleagues investigated the role of t-Darpp, a novel gene that they identified in the most commonly altered DNA region in gastric cancers.

The investigators detected high levels of t-Darpp in two thirds of primary gastric adenocarcinomas. Using cell culture models, they demonstrated that expression of t-Darpp increased levels and activity of Akt kinase, a protein that is hyperactivated in a wide range of human tumors. They also showed that t-Darpp blocks cell suicide programs — and promotes cell survival — by increasing the expression of the pro-survival protein Bcl2.

The findings, reported in the Jan. 15 Cancer Research, support a novel role for t-Darpp in gastric cancer development and resistance to chemotherapy-induced cell death.

— Leigh MacMillan

Patching the heart

Stem cell-based therapies to improve cardiac function after a heart attack are currently being tested, but the effectiveness of these approaches is limited by the poor retention of transplanted cells in the heart. Igor Feoktistov, M.D., Ph.D., and colleagues explored the possibility that adenosine — known to be elevated at sites of ischemia and to stimulate blood vessel growth — might enhance stem cell adhesion to the inner lining of the heart and blood vessels (endothelium).

They report in the Feb. 15 Circulation Research that adenosine promotes adhesion of mouse embryonic endothelial progenitor cells (EPCs) to mouse cardiac endothelial cells in culture and that it works through different adenosine receptors on the two cell types (A1 and A2B receptors, respectively). Adenosine also increased adhesion of human EPCs to human cardiac cells and of mouse EPCs to blood vessels in isolated, perfused mouse hearts. The findings suggest that adenosine, which is clinically available, might improve delivery of therapeutic stem cells to the heart.

— Leigh MacMillan

Help for healing

Wounds normally heal, but they often leave unsightly scars that constrict movement and can interfere with normal tissue function. Some tissues are unable to heal, or regenerate, at all. Now, a mouse strain that can re-grow excised ear tissue is providing clues to the factors that favor tissue regeneration over scarring.

Lillian Nanney, Ph.D., Jeffrey Davidson, Ph.D., and colleagues used a proteomic technique to compare protein profiles of healing ear wounds from these regenerative “MRL” mice and standard lab mice. This tissue profiling, performed 4 or 7 days after injury, revealed distinct differences in the types, timing and levels of proteins expressed, particularly in a set of calcium-binding proteins with known regulatory functions in chemotaxis, signal transduction, inflammation and cellular stress.

The results, reported online in Wound Repair and Regeneration, may improve understanding of wound healing and reveal new therapeutic targets to convert undesirable scarring and contraction after injury into a fully restored and regenerated skin that is as good as new.

— Melissa Marino

Recipe for pancreatic islets

Pancreatic islet transplantation has proven a successful treatment for replacing insulin-producing beta-cells in patients with Type 1 diabetes. But a shortage of donor tissue necessitates generating functional islets in vitro, which will require a better understanding of the factors that guide islet development.

To determine factors critical for proper islet formation, Maureen Gannon, Ph.D., and colleagues took advantage of a diabetic mouse model that overexpresses the transcription factor Hnf6 and exhibits abnormal islet growth. In the February issue of PLoS One, they identify differences in gene profiles between wild-type and Hnf6-overexpressing mice during stages important for islet formation. Specifically, the diabetic mice showed differential expression of novel factors neuronatin, regenerating gene 2, and serpina6, as well as genes associated with cell adhesion, migration and proliferation.

Not only does this study identify potential downstream targets of Hnf6, but it also identifies novel factors critical for islet formation. Both findings add a new layer of understanding to pancreas development, islet architecture, and mature beta-cell function.

— Susanne Tranguch

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012