MiR-21 is continually elevated long-term in the brain after exposure to ionizing radiation.
Ionizing radiation stimulates miR-21 expression in different types of mammalian cells in culture. However, it remains unclear whether radiation could stimulate miR-21 expression in brain cells and tissue and, if so, how long the upregulation of miR-21 would be maintained after exposure to different types of radiation. To answer these questions, we examined the miR-21 levels in irradiated mouse hippocampal cells and brain tissue from mice at different times up to 1 year after whole-body exposure to 0.5 Gy of X rays [low linear energy transfer (LET)] or (56)Fe ions (high LET). The results showed that radiation stimulated miR-21 expression in mouse hippocampal cells and upregulation of EGFR, which is similar to that in human hepatocytes, as we reported previously. Interestingly, the miR-21 levels gradually increased within 1 year after irradiation, although there was no significant difference in the miR-21 low- and high-LET irradiated mice. The high expression of miR-21 in the brain was also associated with high expression of EGFR in irradiated mice; thus our data strongly support that EGFR and miR-21 are in a positive regulatory loop, because it is known that radiation stimulates miR-21 through the EGFR/Stat3 pathway and miR-21 activates the EGFR pathway. Since the brain is relatively resistant to radiation-induced histomorphological changes, our findings may provide a new way to explore radiation-induced pathological changes in the brain by investigating miR-21 and its multiple targets.
Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, China.
Yan
Y
Shi
Xiangming
X
Zhang
Xiaobing
X
Tang
Ping
P
Wang
Huichen
H
Wang
Ya
Y
Wang
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors
C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs