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상피세포에서 DNA 손상 저해를 통한 TGF-beta1의 방사선 손상 보호 효과

Title
상피세포에서 DNA 손상 저해를 통한 TGF-beta1의 방사선 손상 보호 효과
Other Titles
TGF-beta1 Protects Epithelial Cells from gamma-Radiation-Induced Apoptosis by Attenuating DNA Damage Responses
Author
김미라
Alternative Author(s)
Kim, Mi Ra
Advisor(s)
신인철
Issue Date
2011-02
Publisher
한양대학교
Degree
Master
Abstract
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates various cellular responses on a variety of cell types. Several groups have suggested that TGF-beta regulates activation of DNA-damage response upon irradiation, which results in either cell survival or apoptosis depending on the cellular context. However, how TGF-beta controls the cell fate upon irradiation has not been fully understood yet. In the present study, we investigated the effects of TGF-beta1 on DNA-damage responses and cell death by irradiation in epithelial cells. Twenty-four hour pretreatment of TGF-beta1 protected cells from apoptosis in response to irradiation based on Annexin V staining and DNA fragmentation. Consistently, reduced activations of Caspase-9 and Caspase-3 and cleavage of PARP were detected in TGF-beta1-pretreated A431 and HaCaT cells. To explore possible mechanisms for the apoptosis, we examined the DNA damage response. Six and twenty-four hour after irradiation, length of comet tail, gamma-H2AX foci formation, and phosphorylation of ATM, Chk2, and p53 were reduced by TGF-beta1 treatment. Type I TGF-beta receptor (TbRI) inhibitor, SB431542, inhibited these radio-protective effect of TGF-beta1 on three dimensional culture and in vivo study. Overall, these data suggest that TGF-beta1 protects cells from gamma-irradiation-induced apoptosis by attenuating DNA damage.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/140027http://hanyang.dcollection.net/common/orgView/200000416409
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > LIFE SCIENCE(생명과학과) > Theses (Master)
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