| First Author | Zhang Y | Year | 2015 |
| Journal | Sci Transl Med | Volume | 7 |
| Issue | 290 | Pages | 290ra92 |
| PubMed ID | 26041709 | Mgi Jnum | J:234073 |
| Mgi Id | MGI:5788850 | Doi | 10.1126/scitranslmed.3010228 |
| Citation | Zhang Y, et al. (2015) Drug-induced regeneration in adult mice. Sci Transl Med 7(290):290ra92 |
| abstractText | Whereas amphibians regenerate lost appendages spontaneously, mammals generally form scars over the injury site through the process of wound repair. The MRL mouse strain is an exception among mammals because it shows a spontaneous regenerative healing trait and so can be used to investigate proregenerative interventions in mammals. We report that hypoxia-inducible factor 1alpha (HIF-1alpha) is a central molecule in the process of regeneration in adult MRL mice. The degradation of HIF-1alpha protein, which occurs under normoxic conditions, is mediated by prolyl hydroxylases (PHDs). We used the drug 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), a PHD inhibitor, to stabilize constitutive expression of HIF-1alpha protein. A locally injectable hydrogel containing 1,4-DPCA was designed to achieve controlled delivery of the drug over 4 to 10 days. Subcutaneous injection of the 1,4-DPCA/hydrogel into Swiss Webster mice that do not show a regenerative phenotype increased stable expression of HIF-1alpha protein over 5 days, providing a functional measure of drug release in vivo. Multiple peripheral subcutaneous injections of the 1,4-DPCA/hydrogel over a 10-day period led to regenerative wound healing in Swiss Webster mice after ear hole punch injury. Increased expression of the HIF-1alpha protein may provide a starting point for future studies on regeneration in mammals. |
