Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity

Nikolett Sándor, Boglárka Schilling-Tóth, Eniko Kis, Anett Benedek, Katalin Lumniczky, G. Sáfrány, H. Hegyesi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100 mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells.

Original languageEnglish
Pages (from-to)142-149
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume793
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Growth Differentiation Factor 15
Radiation Tolerance
Radiation
Fibroblasts
Cell Line
Small Interfering RNA
Cell Cycle
Bystander Effect
Fibroblast Growth Factors
R Factors
Telomerase

Keywords

  • Cell cycle
  • GDF-15 gene
  • Human fibroblast
  • Radiation targets
  • Radiosensitivity
  • RNA interference

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity. / Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Eniko; Benedek, Anett; Lumniczky, Katalin; Sáfrány, G.; Hegyesi, H.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 793, 01.11.2015, p. 142-149.

Research output: Contribution to journalArticle

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AU - Benedek, Anett

AU - Lumniczky, Katalin

AU - Sáfrány, G.

AU - Hegyesi, H.

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