Neuregulin-1 accelerates corneal epithelial wound healing

Growth Factors. 2017 Dec;35(6):225-233. doi: 10.1080/08977194.2018.1436055. Epub 2018 Feb 20.


Corneal epithelial cells (CECs) play an important role in the function of the cornea, and are maintained by corneal epithelial stem cells (CESCs). Recent studies have shown that neuronal growth factors affect the proliferation and migration of CESCs. Neuregulin-1 (NR-1) is a neuronal growth factor that is expressed in the early stages of brain development. The aim of this study was to determine whether NR-1 activates corneal wound healing. We observed that NR-1 activated both proliferation and migration of CECs. In addition, the colony-forming efficacy of CESCs was enhanced. In mice, NR-1 treatment improved corneal wound healing. Furthermore, the expression of markers of corneal epithelium maintenance (ΔNp63) and CESC proliferation (Bmi-1 and Abcg2) was increased. These effects were mediated by intracellular signalling pathways (Stat3, Erk1/2 and p38). Taken together, our results suggest that NR-1 accelerates the recovery of corneal wounds, and may represent a novel treatment for corneal damage.

Keywords: Neuregulin-1; cell migration; corneal cell; proliferation; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Animals
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Corneal Injuries / drug therapy*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neuregulin-1 / pharmacology*
  • Neuregulin-1 / therapeutic use
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • STAT3 Transcription Factor / metabolism
  • Wound Healing / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Abcg2 protein, mouse
  • Bmi1 protein, mouse
  • Neuregulin-1
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • Polycomb Repressive Complex 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases