Low-dose γ-irradiation induces dual radio-adaptive responses depending on the post-irradiation time by altering microRNA expression profiles in normal human dermal fibroblasts

Bae,Seunghee; Kim,Karam; Cha,Hwa Jun; Choi,Yeongmin; Shin,Shang Hun; An,In-Sook; Lee,Jae  Ho; Lee,Su Jae; Kim,Ji Young; Nam,Seon Young; An,Sungkwan

doi:10.3892/ijmm.2014.1994

Low-dose γ-irradiation induces dual radio-adaptive responses depending on the post-irradiation time by altering microRNA expression profiles in normal human dermal fibroblasts

Authors:
- Seunghee Bae
- Karam Kim
- Hwa Jun Cha
- Yeongmin Choi
- Shang Hun Shin
- In-Sook An
- Jae Ho Lee
- Su Jae Lee
- Ji Young Kim
- Seon Young Nam
- Sungkwan An
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Affiliations: Molecular-Targeted Drug Research Center and Korea Institute for Skin and Clinical Sciences, Konkuk University, Seoul 143-701, Republic of Korea, Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine, Seoul 100-380, Republic of Korea, Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea, Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Seoul 132-703, Republic of Korea
Published online on: November 10, 2014 https://doi.org/10.3892/ijmm.2014.1994
Pages: 227-237

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Abstract

Exposure to high-dose ionizing radiation, including γ-radiation, induces severe skin disorders. However, the biological consequences and molecular mechanisms responsible for the response of human skin to low-dose γ-radiation (LDR) are largely unknown. In the present study, we demonstrate that LDR (0.1 Gy) induces distinct cellular responses in normal human dermal fibroblasts (NHDFs) depending on the post-irradiation time point. A MTT-based cell viability assay and propidium iodide staining-based cell cycle assay revealed that the viability and proportion of the cells in the G2/M phase were differed at 6 and 24 h post-irradiation. Reverse transcription quantitative PCR (RT-qPCR) revealed that LDR significantly upregulated the mRNA expression of collagen type I alpha 1 (COL1A1), but downregulated the mRNA expression of matrix metalloproteinase 1 (MMP1) at 24 h post-irradiation. MicroRNA (miRNA) microarray analysis further demonstrated that LDR induced changes in the expression profiles of specific miRNAs and that some of the deregulated miRNAs were specific to either the early or late radio-adaptive response. Our results suggest that LDR generates dual radio-adaptive responses depending on the post-irradiation time by altering specific miRNA expression profiles in NHDFs.

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1	Nguyen PK and Wu JC: Radiation exposure from imaging tests: is there an increased cancer risk? Expert Rev Cardiovasc Ther. 9:177–183. 2011. View Article : Google Scholar : PubMed/NCBI
2	Cleaver JE: Biology and genetics in the biological effects of ionizing radiation (BEIR VII) report. Health Physics. 89:S32. 2005.
3	Feinendegen LE: Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiol. 78:3–7. 2005. View Article : Google Scholar : PubMed/NCBI
4	Sjerobabski-Masnec I and Situm M: Skin aging. Acta Clin Croat. 49:515–518. 2010.
5	Gelse K, Pöschl E and Aigner T: Collagens - structure, function, and biosynthesis. Adv Drug Deliv Rev. 55:1531–1546. 2003. View Article : Google Scholar : PubMed/NCBI
6	Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ and Fisher GJ: Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc. 14:20–24. 2009. View Article : Google Scholar : PubMed/NCBI
7	Constable PH, Crowston JG, Occleston NL and Khaw PT: The effects of single doses of beta radiation on the wound healing behaviour of human Tenon’s capsule fibroblasts. Br J Ophthalmol. 88:169–173. 2004. View Article : Google Scholar : PubMed/NCBI
8	Rastogi RP, Richa, Kumar A, Tyagi MB and Sinha RP: Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids. 2010:5929802010. View Article : Google Scholar
9	Chang TC, Wentzel EA, Kent OA, et al: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 26:745–752. 2007. View Article : Google Scholar : PubMed/NCBI
10	He L, He X, Lim LP, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI
11	Liu C, Zhou C, Gao F, et al: MiR-34a in age and tissue related radio-sensitivity and serum miR-34a as a novel indicator of radiation injury. Int J Biol Sci. 7:221–233. 2011. View Article : Google Scholar : PubMed/NCBI
12	Joly-Tonetti N, Viñuelas J, Gandrillon O and Lamartine J: Differential miRNA expression profiles in proliferating or differentiated keratinocytes in response to gamma irradiation. BMC Genomics. 14:1842013. View Article : Google Scholar : PubMed/NCBI
13	Cha HJ, Seong KM, Bae S, et al: Identification of specific microRNAs responding to low and high dose γ-irradiation in the human lymphoblast line IM9. Oncol Rep. 22:863–868. 2009.PubMed/NCBI
14	Cha HJ, Shin S, Yoo H, et al: Identification of ionizing radiation-responsive microRNAs in the IM9 human B lymphoblastic cell line. Int J Oncol. 34:1661–1668. 2009.PubMed/NCBI
15	Cha HJ, Lee KS, Lee GT, et al: Altered miRNA expression profiles are involved in the protective effects of troxerutin against ultraviolet B radiation in normal human dermal fibroblasts. Int J Mol Med. 33:957–963. 2014.PubMed/NCBI
16	Paraskevopoulou MD, Georgakilas G, Kostoulas N, et al: DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res. 41:W169–W173. 2013. View Article : Google Scholar : PubMed/NCBI
17	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
18	Kraemer A, Anastasov N, Angermeier M, Winkler K, Atkinson MJ and Moertl S: MicroRNA-mediated processes are essential for the cellular radiation response. Radiat Res. 176:575–586. 2011. View Article : Google Scholar : PubMed/NCBI
19	Huang Y, Shen XJ, Zhou Q, Wang SP, Tang SM and Zhang GZ: Biological functions of microRNAs: a review. J Physiol Biochem. 67:129–139. 2011. View Article : Google Scholar
20	Fernet M, Mégnin-Chanet F, Hall J and Favaudon V: Control of the G2/M checkpoints after exposure to low doses of ionising radiation: implications for hyper-radiosensitivity. DNA Repair (Amst). 9:48–57. 2010. View Article : Google Scholar
21	Varga J and Abraham D: Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 117:557–567. 2007. View Article : Google Scholar : PubMed/NCBI
22	Wei LC, Ding YX, Liu YH, et al: Low-dose radiation stimulates Wnt/β-catenin signaling, neural stem cell proliferation and neurogenesis of the mouse hippocampus in vitro and in vivo. Curr Alzheimer Res. 9:278–289. 2012. View Article : Google Scholar : PubMed/NCBI