Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway

Abstract

Previous studies have shown that carbon monoxide (CO) is involved in a variety of physiological and pathophysiological processes including anti-inflammatory, anti-apoptotic and anti-oxidant responses. However, it remains unclear whether CO promotes gastric ulcer healing. In the present study, we evaluated the efficacy of CO-saturated saline in the treatment of gastric ulcers and its underlying mechanism. Acute gastric ulcers were induced in C57BL/6 male mice using acetic acid. A CO-saturated solution was prepared by bubbling 50% CO gas into saline. To investigate the effect of CO on gastric mucosal healing, CO solution was orally administrated twice a day beginning on day 3 after the induction of gastric ulcer. Mice were sacrificed on day 7 after ulcer induction. The stomach was removed, and the ulcerated lesions were measured. In vitro wound healing assays were used to determine the mechanism of action of CO in the restoration of murine gastric epithelial cells. The oral administration of CO solution accelerated the gastric ulcer healing by promoting re-epithelialization. Furthermore, the wound healing assay performed using the murine gastric epithelial cells revealed that the CO-saturated medium enhanced cell migration through the activation of protein kinase C (PKC). Based on these data, CO may represent a novel therapeutic approach for the treatment of gastric mucosal injuries.

Keywords:

• Carbon monoxide
• gastric ulcer
• protein kinase C
• re-epithelialization
• wound healing

Disclosure statement

Yuji Naito received scholarship funds from Otsuka Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to declare.

Funding information

This work was supported by a Grant-in-Aid for Scientific Research (C) to Tomohisa Takagi (Grant no. 25460959) and (C) to Yuji Naito (Grant no. 25460958) from the Japan Society for the Promotion of Science.