Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Cell Signal. 2013 Dec;25(12):2374-82. doi: 10.1016/j.cellsig.2013.07.029. Epub 2013 Aug 3.


Nitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMP-dependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).

Keywords: Cell migration; ERK; NO; NO-Cbi; Nitric oxide; PDE; PKG; SNP; Src; Wound healing; cGMP-dependent protein kinase; extracellular signal regulated kinase; nitrosyl-cobinamide; phosphodiesterase; sodium nitroprusside.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Cobamides / chemistry
  • Cobamides / pharmacology*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Lung / cytology
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology*
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / pharmacology*
  • Signal Transduction / drug effects
  • Wound Healing / drug effects*


  • Cobamides
  • Nitric Oxide Donors
  • Nitrogen Oxides
  • cobinamide
  • Cyclic GMP-Dependent Protein Kinases