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Publications (3)11.75 Total impact

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    ABSTRACT: Several groups have reported that transforming growth factor-beta1 (TGF-beta1) regulates cellular responses to gamma-irradiation; however, the exact mechanism has not been fully elucidated. In the present study, the role of TGF-beta1 in cellular responses to gamma-irradiation was investigated in detail. The data indicate that TGF-beta1 pretreatment decreased the aftermath of ionizing radiation (IR)-induced DNA damage in a SMAD-dependent manner. To determine the underlying mechanism for these effects, the extent of IR-induced DNA repair activity in the presence or absence of TGF-beta1 was examined. Studies reveal that TGF-beta1 up-regulated DNA ligase IV (LIG4), augmented IR-induced nuclear retention of the DNA ligase, and enhanced non-homologous end-joining (NHEJ) repair activity. In addition, knockdown of LIG4 reduced the TGF-beta1-induced protection against IR. Overall, these data indicate that TGF-beta1 facilitates the NHEJ repair process upon gamma-irradiation and thereby enhances long-term survival. Implications: These findings provide new insight and a possible approach to controlling genotoxic stress by the TGF-beta signaling pathway.
    Molecular Cancer Research 10/2014; 13(2). DOI:10.1158/1541-7786.MCR-14-0098-T · 4.50 Impact Factor
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    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.
    Experimental Cell Research 12/2012; DOI:10.1016/j.yexcr.2012.12.008 · 3.37 Impact Factor
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    ABSTRACT: The therapeutic use of ionizing radiation (e.g., X-rays and γ-rays) needs to inflict minimal damage on non-target tissue. Recent studies have shown that substance P (SP) mediates multiple activities in various cell types, including cell proliferation, anti-apoptotic responses, and inflammatory processes. The present study investigated the effects of SP on γ-irradiated bone marrow stem cells (BMSCs). In mouse bone marrow extracts, SP prolonged activation of Erk1/2 and enhanced Bcl-2 expression, but attenuated the activation of apoptotic molecules (e.g., p38 and cleaved caspase-3) and down-regulated Bax. We also observed that SP-decreased apoptotic cell death and stimulated cell proliferation in γ-irradiated mouse bone marrow tissues through TUNEL assay and PCNA analysis. To determine how SP affects bone marrow stem cell populations, mouse bone marrow cells were isolated and colony-forming unit (CFU) of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) was estimated. SP-pretreated ones showed higher CFUs of MSC and HSC than untreated ones. Furthermore, when SP was pretreated in cultured human MSC, it significantly decreased apoptotic cells at 48 and 72 h after γ-irradiation. Compared with untreated cells, SP-treated human MSCs showed reduced cleavage of apoptotic molecules such as caspase-8, -9, -3, and poly ADP-ribose polymerase (PARP). Thus, our results suggest that SP alleviates γ-radiation-induced damage to mouse BMSCs and human MSCs via regulation of the apoptotic pathway.
    Journal of Cellular Physiology 05/2011; 226(5):1204-13. DOI:10.1002/jcp.22447 · 3.87 Impact Factor