Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms18102103
Keywords
radiation enteropathy; endothelial dysfunction; geranylgeranylacetone (GGA); angiogenesis
Funding
- Nuclear Research and Development Program of the National Research Foundation of Korea (NRF) [NRF-2015M2B2B1068627, 2015R1C1A1A01053531]
- Korea Institute of Radiological and Medical Sciences - Korean Government Ministry of Science, ICT, & Future Planning [KIRAMS/1711045557, 1711045538, 1711045554/50531-2017]
- National Research Foundation of Korea [2015M2B2B1068627, 2015R1C1A1A01053531] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Radiation-induced intestinal toxicity is common among cancer patients after radiotherapy. Endothelial cell dysfunction is believed to be a critical contributor to radiation tissue injury in the intestine. Geranylgeranylacetone (GGA) has been used to treat peptic ulcers and gastritis. However, the protective capacity of GGA against radiation-induced intestinal injury has not been addressed. Therefore, we investigated whether GGA affects intestinal damage in mice and vascular endothelial cell damage in vitro. GGA treatment significantly ameliorated intestinal injury, as evident by intestinal crypt survival, villi length and the subsequently prolonged survival time of irradiated mice. In addition, intestinal microvessels were also significantly preserved in GGA-treated mice. To clarify the effect of GGA on endothelial cell survival, we examined endothelial function by evaluating cell proliferation, tube formation, wound healing, invasion and migration in the presence or absence of GGA after irradiation. Our findings showed that GGA plays a role in maintaining vascular cell function; however, it does not protect against radiation-induced vascular cell death. GGA promoted endothelial function during radiation injury by preventing the loss of VEGF/VEGFR1/eNOS signaling and by down-regulating TNF alpha expression in endothelial cells. This finding indicates the potential impact of GGA as a therapeutic agent in mitigating radiation-induced intestinal damage.
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