Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. It has been reported that hydrogen sulfide (H2S) has pro-angiogenic effects. We hypothesize that H2S improves diabetic wound healing via restoring endothelial progenitor cell (EPC) function in type 2 diabetes. The Db/db mice were treated with sodium hydrosulfide (NaHS), 4-hydro- xythiobenzamide group (HTB), or saline for 18 days, respectively. Db/+ mice were treated with either DL-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared to the diabetic control group. Wound closure rates in the NaHS and HTB groups were significantly faster than those of the db/db group, in which the PAG group had slower wound closure rates. Wound skin capiliary densities were enhanced in the NaHS and HTB groups. The EPC functions were significantly preserved in the NaHS and HTB groups, but decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were up-regulated in the NaHS and HTB groups compared to db/db controls, but down-regulated by in vivo PAG and in vitro si-CSE treatment compared to normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 siRNA before NaHS treatment compared to db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing via restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.
Drs. Fang Liu and Dan-Dan Chen share first authorship
- Received March 31, 2013.
- Accepted January 22, 2014.
- © 2014 by the American Diabetes Association.
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