Let-7 microRNAs regenerate peripheral nerve regeneration by targeting nerve growth factor

Mol Ther. 2015 Mar;23(3):423-33. doi: 10.1038/mt.2014.220. Epub 2014 Nov 14.


Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Coculture Techniques
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nerve Growth Factor / agonists
  • Nerve Growth Factor / genetics*
  • Nerve Growth Factor / metabolism
  • Nerve Regeneration / genetics*
  • Neurons / cytology
  • Neurons / metabolism
  • Peripheral Nerve Injuries / genetics
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy*
  • Primary Cell Culture
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism*
  • Sciatic Nerve / pathology
  • Signal Transduction
  • Transfection


  • MIRNLET7 microRNA, rat
  • MicroRNAs
  • RNA, Small Interfering
  • Nerve Growth Factor