McGowan Institute for Regenerative Medicine
faculty member Ivet Bahar, PhD (pictured), John K. Vries Chair and professor in the Department of Computational Biology, and professor in Molecular Genetics and Biochemistry, along with a team of University of Pittsburgh researchers, have identified and described an enzyme inhibitor that allows them to increase the number of cardiac progenitor cells and therefore influence the size of the developing heart. The scientists used a zebrafish model that has powerful advantages for studying embryonic development.
Through the study of developmental biology the researchers gained a better understanding of the developing heart. Knowing the biologic pathways and signals that formed these organs whole and healthy in the first place will help as they try to create treatments that restore normal function to adult damaged or diseased tissues.
Zebrafish are vertebrate animals whose transparent embryos develop rapidly, are small and easy to handle and, most importantly, grow outside of the mother. In earlier work, scientists bred a line of transgenic zebrafish with the gene for green fluorescent protein linked to a key signaling pathway of fibroblast growth factors (FGFs), a family of proteins that are essential in embryonic development.
For the current paper, the research team focused on a small molecule called BCI, which hyperactivated FGF signaling. They then figured out how: BCI blocked the activity of an enzyme called Dusp6, a feedback regulator that would otherwise have tamped down the enhanced FGF signal.
Knowing that, BCI could then be used as a tool to find out what effect Dusp6 inhibition would have on heart development. The team reported that zebrafish treated with BCI had a greater number of cardiac progenitor cells and, ultimately, larger hearts.
Also, unraveling the fibroblast growth factor pathway has broad implications for improving wound healing. For example, FGF2 has been used in treatment of chronic skin ulcers and following burn surgery in Japan. Thus, BCI alone or in combination with FGF2 might accelerate the healing process and improve wound repair.
Illustration: McGowan Institute for Regenerative Medicine.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (07/05/09)
Genetic Engineering & Biotechnology News (07/05/09)
Medical News Today (07/06/09)
Bio: Dr. Ivet Bahar
Abstract (Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Ivet Bahar, et al. National Chemical Biology, Published online: 5 July 2009)