The role of mTOR signaling in hair follicle repair in response to ionizing radiation damage in mice
Date Issued
2015
Date
2015
Author(s)
Chien, Ting-Han
Abstract
Radiotherapy is one of the commonly used in cancer treatment. By use of ionizing radiation (IR), radiotherapy can kill cancer cells inside our bodies. However, IR can also cause damage to adjacent healthy tissues, resulting in various acute or chronic side effects. One of the most annoying side effects to is IR-induced alopecia, which is often seen after radiotherapy for head and neck neoplasm. There is currently no efficient treatment for IR-induced alopecia. mTOR signaling is a well-known signaling pathway responding to growth factors, nutrients, oxygen and energy level. mTOR signaling has been reported to be involved in regeneration processes in skin and hair. Whether mTOR can be a possible molecular target to prevent IR-induced alopecia is unknown. Here we explored this possibility. Thirty two-day-old C57BL/6 mice were given mTOR inhibitor rapamycin and then exposed to IR. At 4 Gy of IR, inhibition of mTOR signaling resulted in more severe alopecia in 5 days. Histological analysis showed more severe hair follicle shortening and dystrophy. The self-repair for hair dystrophy was impaired. Further analysis showed that inhibition of mTOR signaling did not increased apoptosis but reduced cell proliferation with increased cell cycle arrest. In addition, differentiation of hair follicle was also compromised. Increased DNA damage intense at early time points after IR exposure was also observed. For molecular signaling, we found mTOR inhibition might inhibit the repair process by affecting Wnt signaling activity. This research demonstrated the possible role of mTOR signaling in hair follicle repair in response to IR.
Subjects
radiotherapy
alopecia
mTOR signaling
rapamycin
DNA damage response
SDGs
Type
thesis
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