Regulation of neovascularization by S-glutathionylation via the Wnt5a/sFlt-1 pathway

Colin E. Murdoch*, Markus M. Bachschmid, Reiko Matsui

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


S-glutathionylation occurs when reactive oxygen or nitrogen species react with protein-cysteine thiols. Glutaredoxin-1 (Glrx) is a cytosolic enzyme which enzymatically catalyses the reduction in S-glutathionylation, conferring reversible signalling function to proteins with redox-sensitive thiols. Glrx can regulate vascular hypertrophy and inflammation by regulating the activity of nuclear factor κB (NF-κB) and actin polymerization. Vascular endothelial growth factor (VEGF)-induced endothelial cell (EC) migration is inhibited by Glrx overexpression. In mice overexpressing Glrx, blood flow recovery, exercise function and capillary density were significantly attenuated after hindlimb ischaemia (HLI). Wnt5a and soluble Fms-like tyrosine kinase-1 (sFlt-1) were enhanced in the ischaemic-limb muscle and plasma respectively from Glrx transgenic (TG) mice. A Wnt5a/sFlt-1 pathway had been described in myeloid cells controlling retinal blood vessel development. Interestingly, a Wnt5a/sFlt-1 pathway was found also to play a role in EC to inhibit network formation. S-glutathionylation of NF-κB components inhibits its activation. Up-regulated Glrx stimulated the Wnt5a/sFlt-1 pathway through enhancing NF-κB signalling. These studies show a novel role for Glrx in post-ischaemic neovascularization, which could define a potential target for therapy of impaired angiogenesis in pathological conditions including diabetes.

Original languageEnglish
Pages (from-to)1665-1670
Number of pages6
JournalBiochemical Society Transactions
Issue number6
Publication statusPublished - Dec 2014

Bibliographical note

This research was originally published in Biochemical Society transactions. Murdoch, C. E., Bachschmid, M. M., & Matsui, R. Regulation of neovascularization by S-glutathionylation via the Wnt5a/sFlt-1 pathway. Biochemical Society transactions. 2014; 42:1665-1670. © the Biochemical Society


  • angiogenesis
  • glutaredoxin
  • S-glutathionylation
  • nuclear factor κB (NF-κB), soluble Fms-like tyrosine kinase-1 (sFlt-1)
  • Wnt5a


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