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Title: TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

Abstract

The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV.more » •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22598795
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 476; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL PATHWAYS; BIOLOGICAL REPAIR; DNA; DNA DAMAGES; GROWTH FACTORS; HISTONES; IN VIVO; IRRADIATION; LIGASES; RECEPTORS; SIGNALS

Citation Formats

Lee, Jeeyong, Kim, Mi-Ra, Kim, Hyun-Ji, An, You Sun, and Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr. TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.136.
Lee, Jeeyong, Kim, Mi-Ra, Kim, Hyun-Ji, An, You Sun, & Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr. TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling. United States. doi:10.1016/J.BBRC.2016.05.136.
Lee, Jeeyong, Kim, Mi-Ra, Kim, Hyun-Ji, An, You Sun, and Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr. Fri . "TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling". United States. doi:10.1016/J.BBRC.2016.05.136.
@article{osti_22598795,
title = {TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling},
author = {Lee, Jeeyong and Kim, Mi-Ra and Kim, Hyun-Ji and An, You Sun and Yi, Jae Youn, E-mail: yjy_71@kcch.re.kr},
abstractNote = {The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.},
doi = {10.1016/J.BBRC.2016.05.136},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 476,
place = {United States},
year = {Fri Aug 05 00:00:00 EDT 2016},
month = {Fri Aug 05 00:00:00 EDT 2016}
}