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Archive - Apr 5, 2010

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Vascularization Pathway Mediated by MicroRNA Is Discovered

Researchers at the University of Massachusetts Medical School and colleagues have discovered a critical step for blood vessel growth in zebrafish embryos, providing new insight into how vascular systems develop and offering a potential therapeutic target for preventing tumor growth, which depends on vascularization. The researchers have identified a novel microRNA-mediated genetic pathway responsible for new blood vessel growth (angiogenesis) in zebrafish embryos. The work provides new insights into how vascular systems use the forces of existing blood flow to initiate the growth of new vessels. Focusing on the development of the fifth and sixth aortic arches in the zebrafish, senior author Dr. Nathan Lawson described how the forces exerted by blood flow on endothelial cells are a critical component for expressing a microRNA that triggers new vessel development. In the early stages of development, when blood flow is present in the aortic vessels, but the vascular linkages between the two arches have yet to be established, the stimulus provided by active blood flow leads to expression of an endothelial-cell specific microRNA (mir-126). In turn, this microRNA turns on vascular endothelial growth factor (VEGF), a chemical signal produced by surrounding cells that normally stimulates angiogenesis. Thus, blood flow allows the endothelial cells to respond to VEGF by growing into new blood vessels. However, when blood flow in the aortic arches was restricted, mir-126 failed to be expressed. In the absence of this microRNA, new blood vessels were unable to develop due to a block in VEGF signaling. "We have known for over a hundred years that blood flow makes new vessels grow," said Dr. Lawson. "But we never really knew how cells in a growing vessel interpreted this signal.

Pancreas Alpha-Cells Can Convert to Insulin-Producing Beta-Cells

In a mouse model, scientists have discovered that alpha-cells in the pancreas, which do not produce insulin, can convert into insulin-producing beta-cells, advancing the prospect of regenerating beta-cells as a cure for type 1 diabetes. The research team, led by senior author Dr. Pedro L. Herrera of the University of Geneva, demonstrated that beta-cells will spontaneously regenerate after near-total beta-cell destruction in mice and the majority of the regenerated beta-cells are derived from alpha-cells that had been reprogrammed, or converted, into beta-cells. Using a unique model of diabetes in mice, in which nearly all of the beta-cells are rapidly destroyed, the researchers found that if the mice were maintained on insulin therapy, beta-cells were slowly and spontaneously restored, eventually eliminating the need for insulin replacement. Alpha-cells normally reside alongside beta-cells in the pancreas and secrete a hormone called glucagon, which works in opposition to insulin to regulate the levels of sugar in the blood. Alpha-cells are not attacked by the autoimmune processes that destroy beta-cells and cause type 1 diabetes. Dr. Andrew Rakeman, the Juvenile Diabetes Research Foundation (JDRF) Program Manager in Beta-Cell Therapies and who was not involved in the research, said that the breakthrough in Dr. Herrera's work is the demonstration that alpha-to-beta-cell reprogramming can be a natural, spontaneous process. "If we can understand the signals that are triggering this conversion, it will open a whole new potential strategy for regenerating beta-cells in people with type 1 diabetes," he said. "It appears that the body can restore beta-cell function either through reprogramming alpha-cells to become beta-cells or, as previously shown by others, by increasing growth of existing beta cells.