• Animal cells and systems
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• v.4 no.3
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• pp.273-278
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• 2000

Transforming growth factor-$\beta$ (IGF-$\beta$)s are multifunctional small polypeptides synthesized in most cell types. TGF-$\beta$ exerts pivotal effects on both bone formation and resorption. In addition, increasing lines of evidence implicate TGF-$\beta$ as a potential coupling factor between these two processes during bone remodeling. In the present study, the expression form and the activation mechanism of latent-TGF-$\beta$ were investigated using specific antibodies for each isoform. TGF-$\beta$s were observed to be synthesized and accumulated in a large amount in cultured osteoblastic cells. The estimated molecular weights of intracellular TGF-$\beta$2 and -$\beta$3 were 49 and 55 kDa, respectively. Based on proteolytic digestion study and immunofluorescence observation, these precursor forms seemed to be accumulated in distinct intracellular compartments. To examine whether the internal pool of TGF-$\beta$ was possiblely regulated by external signals, their biological activites were examined in a conditioned media of this cell. Although the intact conditioned media did not contain detectable TGF-$\beta$ activity, heat-treatment or acid-activation of the conditioned media revealed significant TGF-$\beta$ activity. Furthermore, in the presence of estrogen, this activity was dramatically diminished. It is known that activation of latent TGF-$\beta$ can be achieved by different chemical and enzymatic treatments, or by incubation with certain cell types. This extracellular activation was suggested as a key step in the regulation of TGF-$\beta$ activity. In addition to these extracellular activation, this study suggests that the synthesis and intracellular processing are important regulation steps for TGF-$\beta$ action. In addition, this regulation Is specific for TGF-$\beta$ type 2, because the change was not observed in TGF-$\beta$3 in osteoblastic cell line.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.369-376
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• 2008

In the present study, we investigated the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl) on irradiated rat lungs to determine its potential as a radioprotective agent. We found that early lung damage induced by irradiation was reduced by treatment with 40mg/kg of cyclo(L-phenylalanyl-L-prolyl) in the latent and early pneumonitis phases. Expression of $TNF-{\alpha}\;and\;TGF-{\beta}1$ at 2 and TGF-${\beta}1$ at 8 weeks post-irradiation was decreased in animals that received both radiation and cyclo(L-phenylalanyl-L-prolyl) compared with animals that received radiation alone. Evidence indicated that the proinflammatory cytokine TNF-${\alpha}$ and the fibrogenic cytokine TGF-${\beta}1$ likely play a role in the radioprotective effect of cyclo(L-phenylalanyl-L-prolyl). However, besides TNF-${\alpha}$ and TGF-${\beta}1$ expressions, the precise mechanism by which cyclo(L-phenylalanyl-L-prolyl) ameliorates the induced radiation damage is not clear.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.190-198
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• 2001

Purpose : It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We peformed this study to investigate the radioprotective effect and mechanism of Captopril. Methods and Materials : The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains $(TNF\alpha\;and\;TGF\beta1)$ at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. Result : In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the $TNF\alpha$ expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the $TGF\beta1$ expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p<0.02). At 8 weeks, the expression of $TNF\alpha\;and\;TGF\beta1$ of most sites, except $TGF\beta1$ of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. Conclusion : This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of $TNF\alpha\;and\;TGF\beta1$ at 2 weeks and $TGF\beta1$ at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine $(TNF\alpha)$ and fibrogenic cytokine $(TGF\beta1)$ probably play the role of the radioprotective mechanism in Captopril.

• Archives of Plastic Surgery
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• v.45 no.5
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• pp.403-410
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• 2018

Background Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed. Methods The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-${\beta}$), and Western blotting with Wnt-3 and ${\beta}$-catenin. Increases in the levels of TGF-${\beta}$, Wnt, and ${\beta}$-catenin were detected after irradiation. Results All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects. Conclusions This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing.