Editors' ChoiceRegeneration

Driving regeneration in mice

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Sci. Signal.  09 Jun 2015:
Vol. 8, Issue 380, pp. ec155
DOI: 10.1126/scisignal.aac7361

The MRL mouse has enhanced regenerative capacity compared with other mice or other mammals. The markedly increased abundance of hypoxia-inducible factor 1α (HIF-1α) both before and after injury in the MRL mouse could contribute to this enhanced regenerative capacity. Prolyl hydroxylases (PHDs) promote the degradation of HIF-1α. Zhang et al. increased the abundance of HIF-1α with a slow-release hydrogel formulation of a PHD inhibitor at the site of ear hole punch injury in adult Swiss Webster mice. PHD inhibitor treatment promoted ear hole healing with closure, rather than scarring, and induced a pattern of cellular markers similar to that observed in MRL mice during regeneration in response to injury. A small interfering RNA against Hif1a blocked regeneration in both MRL mice and drug-treated Swiss Webster mice, showing that HIF-1α is a central driver of regeneration in mice.

Y. Zhang, I. Strehin, K. Bedelbaeva, D. Gourevitch, L. Clark, J. Leferovich, P. B. Messersmith, E. Heber-Katz, Drug-induced regeneration in adult mice. Sci. Transl. Med. 7, 290ra92 (2015). [Abstract]