TGF-Β signaling plays an important role in resisting γ-irradiation

You Sun An; Mi Ra Kim; Seung Sook Lee; Yun Sil Lee; Eunkyung Chung; Jie Young Song; Jeeyong Lee; Jae Youn Yi

doi:10.1016/j.yexcr.2012.12.008

TGF-Β signaling plays an important role in resisting γ-irradiation

You Sun An, Mi Ra Kim, Seung Sook Lee, Yun Sil Lee, Eunkyung Chung, Jie Young Song, Jeeyong Lee, Jae Youn Yi

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Transforming growth factor-Β1 (TGF-Β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-Β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-Β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-Β receptors, we investigated the involvement of TGF-Β signaling in the effects of γ-irradiation. We found that canonical TGF-Β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-Β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-Β1. Our data thus indicate that TGF-Β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.

Original language	English
Pages (from-to)	466-473
Number of pages	8
Journal	Experimental Cell Research
Volume	319
Issue number	4
DOIs	https://doi.org/10.1016/j.yexcr.2012.12.008
State	Published - 15 Feb 2013

Bibliographical note

Funding Information:
We would like to thank Dr. Harold L. Moses (Vanderbilt University, TN, USA) for support in application of R1B and DR26 cell lines. We also thank Dr. Carlos L. Arteaga (Vanderbilt University, TN, USA) for providing various constructs. This work was supported by Nuclear Research & Development Program of Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST), and Basic Science Research Program of National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant no. 2012R1A1A2050560 ).

Keywords

Apoptosis
DNA damage
Smad
TGF-Β1
γ-irradiation

Access to Document

10.1016/j.yexcr.2012.12.008

Cite this

@article{10b6b814ef004fea8ccf697dc4535ca4,

title = "TGF-Β signaling plays an important role in resisting γ-irradiation",

abstract = "Transforming growth factor-Β1 (TGF-Β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-Β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-Β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-Β receptors, we investigated the involvement of TGF-Β signaling in the effects of γ-irradiation. We found that canonical TGF-Β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-Β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-Β1. Our data thus indicate that TGF-Β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.",

keywords = "Apoptosis, DNA damage, Smad, TGF-Β1, γ-irradiation",

author = "An, {You Sun} and Kim, {Mi Ra} and Lee, {Seung Sook} and Lee, {Yun Sil} and Eunkyung Chung and Song, {Jie Young} and Jeeyong Lee and Yi, {Jae Youn}",

note = "Funding Information: We would like to thank Dr. Harold L. Moses (Vanderbilt University, TN, USA) for support in application of R1B and DR26 cell lines. We also thank Dr. Carlos L. Arteaga (Vanderbilt University, TN, USA) for providing various constructs. This work was supported by Nuclear Research & Development Program of Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST), and Basic Science Research Program of National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant no. 2012R1A1A2050560 ). ",

year = "2013",

month = feb,

day = "15",

doi = "10.1016/j.yexcr.2012.12.008",

language = "English",

volume = "319",

pages = "466--473",

journal = "Experimental Cell Research",

issn = "0014-4827",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - TGF-Β signaling plays an important role in resisting γ-irradiation

AU - An, You Sun

AU - Kim, Mi Ra

AU - Lee, Seung Sook

AU - Lee, Yun Sil

AU - Chung, Eunkyung

AU - Song, Jie Young

AU - Lee, Jeeyong

AU - Yi, Jae Youn

N1 - Funding Information: We would like to thank Dr. Harold L. Moses (Vanderbilt University, TN, USA) for support in application of R1B and DR26 cell lines. We also thank Dr. Carlos L. Arteaga (Vanderbilt University, TN, USA) for providing various constructs. This work was supported by Nuclear Research & Development Program of Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST), and Basic Science Research Program of National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant no. 2012R1A1A2050560 ).

PY - 2013/2/15

Y1 - 2013/2/15

N2 - Transforming growth factor-Β1 (TGF-Β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-Β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-Β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-Β receptors, we investigated the involvement of TGF-Β signaling in the effects of γ-irradiation. We found that canonical TGF-Β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-Β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-Β1. Our data thus indicate that TGF-Β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.

AB - Transforming growth factor-Β1 (TGF-Β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-Β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-Β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-Β receptors, we investigated the involvement of TGF-Β signaling in the effects of γ-irradiation. We found that canonical TGF-Β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-Β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-Β1. Our data thus indicate that TGF-Β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival.

KW - Apoptosis

KW - DNA damage

KW - Smad

KW - TGF-Β1

KW - γ-irradiation

UR - http://www.scopus.com/inward/record.url?scp=84875548281&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2012.12.008

DO - 10.1016/j.yexcr.2012.12.008

M3 - Article

C2 - 23262026

AN - SCOPUS:84875548281

SN - 0014-4827

VL - 319

SP - 466

EP - 473

JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 4

ER -

TGF-Β signaling plays an important role in resisting γ-irradiation

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this