XLin28 enhances tissue repair by reprogramming cellular metabolism

Ng Shyh-Chang, Hao Zhu, T. Yvanka De Soysa, Gen Shinoda, Marc T. Seligson, Kaloyan M. Tsanov, Liem Nguyen, John M. Asara, Lewis C. Cantley, George Q. Daley

Research output: Contribution to journalArticle

195 Scopus citations

Abstract

Summary Regeneration capacity declines with age, but why juvenile organisms show enhanced tissue repair remains unexplained. Lin28a, a highly conserved RNA-binding protein expressed during embryogenesis, plays roles in development, pluripotency, and metabolism. To determine whether Lin28a might influence tissue repair in adults, we engineered the reactivation of Lin28a expression in several models of tissue injury. Lin28a reactivation improved hair regrowth by promoting anagen in hair follicles and accelerated regrowth of cartilage, bone, and mesenchyme after ear and digit injuries. Lin28a inhibits let-7 microRNA biogenesis; however, let-7 repression was necessary but insufficient to enhance repair. Lin28a bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos). Lin28a-mediated enhancement of tissue repair was negated by OxPhos inhibition, whereas a pharmacologically induced increase in OxPhos enhanced repair. Thus, Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. PaperClip

Original languageEnglish (US)
Pages (from-to)778
Number of pages1
JournalCell
Volume155
Issue number4
DOIs
StatePublished - Nov 7 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Shyh-Chang, N., Zhu, H., Yvanka De Soysa, T., Shinoda, G., Seligson, M. T., Tsanov, K. M., Nguyen, L., Asara, J. M., Cantley, L. C., & Daley, G. Q. (2013). XLin28 enhances tissue repair by reprogramming cellular metabolism. Cell, 155(4), 778. https://doi.org/10.1016/j.cell.2013.09.059