• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.297-303
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• 2006

Background : Pulmonary tuberculosis is frequently accompanied with complications such as bronchiectasis, cavities, fibrosis and a deterioration of the lung function. However, there is little information available on the pathogenesis of these complications in pulmonary tuberculosis. Among the many factors involving in tissue remodeling, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a potent stimulus of the extracellular matrix fomation and a mediator of potential relevance for airway wall remodeling. Therefore, this study examined the relationship between the radiological changes and the $TGF-{\beta}1$ level in patients with pulmonary tuberculosis. Methods : Serum and bronchoalveolar lavage fluid (BALF) were collected from total of 35 patients before treating them for active pulmonary tuberculosis, and the $TGF-{\beta}1$ levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BALF levels were recalculated as the epithelial lining fluid (ELF) levels using the albumin method. pulmonary function test (PFT) and high resolution computed tomography (HRCT) were performed before and after treatment. Results : There was a strong correlation between the serum $TGF-{\beta}1$ level and the presence of cavities (r=0.404, p=0.006), even though the BAL $TGF-{\beta}1$ level showed a weak correlation with complications. In addition, there was no correlation between the $TGF-{\beta}1$ levels before treatment and the changes in the PFT and HRCT during treatment. Conclusion : There is a correlation between the serum $TGF-{\beta}1$ level and cavity formation in pulmonary tuberculosis before treatment. However, further study will be needed to confirm this.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.438-442
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• 1997

Antisense oligonucleotide represents an interesting tool for selective inhibition of gene expression. However, their low efficiency of introduction within intact cells remains to be overcome. Antisense-$TGF{\beta}$ (25 mer) and antisense-$TGF{\beta}$ (18 mer) were used to study the cellular transport and biological function of antisense oligonucleotide in vitro. Since TGF and TNF play on important role in regulating the nitric oxide production from macrophages, the action of the above antisense oligonucleotides was easily monitored by the determination of nitrite. Poly-L-lysine, benzalkonium chloride and tetraphenylphosphonium chloride were used as polycations, which neutralize the negative charge of antisense oligonucleotide. The production of nitric oxide mediated by .gamma.-IFN in mouse peritoneal macrophage was increased by antisense-TGF.betha. in a dose-dependent manner. Antisense-$TGF{\beta}$ reduced the nitric oxide release from activated RAW 264.7 cells. Significant enhancement in the nitric oxide production was investigated by the cotreatment of poly-L-lysine with antisense-$TGF{\beta}$On the meanwhile, inhibition effect of antisense-$TGF{\beta}$ is not changed by the addition of poly-L-lysine. These results demonstrate that control of expression of $TGF{\beta}$ and TNF.alpha. gene is achieved using antisense technology and the cellular uptake of antisense oligonucleotide could be enhanced by ion-pairing.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.1
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• pp.1-12
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• 1999

The purpose of this study was to evaluate the healing process of the calvarial defect filled with hydroxylapatite(HA) and $TGF-{\beta}$ in Rat. 72 Sprague-Dawly rats were divided into 3 groups, control and two experimental groups. Bony defect were artificially prepared in the calvaria of all 72 rats and followed by implantation of HA (experimental group of 24 rats) and HA+$TGF-{\beta}$(another experimental group of 24 rats) into the defects. Sequential sacrifice was performed at 1, 2, 4, 6, 8, 12 weeks of experiment. Obtained specimen was stained with Hematoxylin and Eosin, Masson's Trichrome and Immunohistochemistry. The results were as follows, 1. Granulation tissue was prominent on control group in 1 and 2 weeks. Bony defects were filled with dense fibrous tissue through the whole experimental period and osteoinduction could not be observed in all groups. 2. Inflammatory cell infiltration was prominent on control group in 1 and 2 weeks and osteoclastic activity was high in HA implanted experimental group at 1 and 2 weeks. 3. Inflammatory cell infiltration was less and maturation of fibrous tissue could be found on HA+$TGF-{\beta}$ implanted experimental group at 1 and 2 weeks. 4. Osteoconduction activity was high in HA+$TGF-{\beta}$ implanted experimental group at 2 and 4 weeks but there was no difference after 6 weeks among 3 groups. 5. In grafted site of HA+$TGF-{\beta}$ implanted group, osteonectin expression was slightly increased from 1 week to 6 weeks. In the host site, it was increased from 1 to 4weeks. 6. In grafted site of HA+$TGF-{\beta}$ implanted group, osteocalcin expression was high at 4 weeks. In the host site, we could find the difference among 3 groups. From above results, the HA with mixture of $TGF-{\beta}$ has the potentiality of promoting bone formation in the bony defect area in the rat.

• Journal of Microbiology and Biotechnology
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• v.12 no.1
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• pp.65-70
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• 2002

A TGF-${\beta}1$/GFP monomeric fusion protein was cloned from pPK9A and pGFP-Cl plasmid by PCR amplification. The fusion protein was expressed in a $Bac-To-Bac^{TM}$ baculovirus expression system. A 45 kDa fusion protein was purified using an Ni-NTA column with 300 mM imidazol from a cell lysate infected with recombinant viruses for 72 h post-infection. The fusion protein cross-reacted with the commercial $TGF-{\beta}1$ polyclonal Ab as well as Ab raised against a precursor, monomeric $TGF-{\beta}1$, and GFP. The binding activity of the fusion protein with a $TGF-{\beta}1$ receptor was examined. Fluorescence was observed in Mv1Lu cells, yet not in insect cells treated with the fusion protein. No fluorescence was detected in Mv1Lu cells incubated with the fusion protein treated with Ab prior to the binding reaction, or with GFP alone, thereby indicating that the binding of the fusion protein was specific to $TGF-{\beta}1$ with a receptor.

• BMB Reports
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• v.41 no.10
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• pp.728-732
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• 2008

FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-${\beta}1$(TGF-${\beta}1$)-induced apoptosis in FaO rat hepatoma cells. TGF-${\beta}1$ caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-${\beta}1$. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-${\beta}1$. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-${\beta}1$ signaling pathway leading to apoptosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.345-354
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• 2000

TGF-${\beta}_1$ is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to wound healing. The objective of this study is to investigate production of TGF-${\beta}_1$ in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of TGF-${\beta}_1$ which may be responsible for wound healing. The fibroblasts were originated from facial dermis and hypertrophic scar in 26 year-old male patient. In the presence of LPS($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$), SEB($0.01{\mu}g$, $0.1{\mu}g$, $1.0{\mu}g$) respectively, cells($5{\times}10^3ml$) were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, cells($2.5{\times}10^5ml$) were cultivated in EMEM with LPS(0.01, 0.1 and $1.0{\mu}g$), SEB(0.01, 0.1 and $1.0{\mu}g$) respectively and LPS($0.1{\mu}g$) and SEB($0.1{\mu}g$) in combination for 24, 48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and TGF-${\beta}_1$ was assayed in duplicate. The results were as follows. 1. In facial dermal fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of TGF-${\beta}_1$ was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. 2. In hypertrophic scar fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell proliferation did not occur at 1 day after incubation, compared with the control. In SEB and LPS exposure in combination, the production of TGF-${\beta}_1$ was increased very significantly at 1 day after incubation, compared with the control. However, the production of TGF-${\beta}_1$ did not occur in SEB and LPS exposure respectively. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of TGF-${\beta}_1$ very significantly and both fibroblasts have different phenotype each other in this regard. This data suggest that the significant production of TGF-${\beta}_1$ may develope abnormal wound healing associated with tissue fibroproliferative disorder, such as hypertrophic scar and keloid formation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2429-2434
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• 2016

Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of $ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and $TGF-{\beta}1$mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of $TGF-{\beta}1$mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and $TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and $TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and $TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.141-148
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• 2015

Epithelial mesenchymal transition (EMT) is the first step in metastasis and implicated in the phenotype of cancer stem cells. Therefore, understanding and controlling EMT, are essential to the prevention and cure of metastasis. In the present study, we examined, by Western blot, reverse transcription polymerase chain reaction (RT-PCR), and confocal microscopy, the effects of cardamonin (CDN) on transforming growth factor-${\beta}1$ (TGF-${\beta}1$)-induced EMT of A549 lung adenocarcinoma cell lines. TGF-${\beta}1$ induced expression of N-cadherin and decreased expression of E-cadherin. CDN suppressed N-cadherin expression and restored E-cadherin expression. Further, TGF-${\beta}1$ induced migration and invasion of A549 cancer cells, which was suppressed by CDN. TGF-${\beta}1$ induced c-Jun N-terminal kinase (JNK) activation during EMT, but CDN blocked it. Protein serine/threonine phosphatase 2A (PP2A) expression in A549 cancer cells was reduced by TGF-${\beta}1$ but CDN restored it. The overall data suggested that CDN suppresses TGF-${\beta}1$-induced EMT via PP2A restoration, making it a potential new drug candidate that controls metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.4
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• pp.414-434
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• 1997

Though many genetic and epigenetic alterations have been identified in hamster oral carcinogenesis model, there is no information about the possible role of transforming growth factor related with oral cancer. The purpose of this paper was to find the expression patterns of transforming growth factor alpha and beta during the stages of complete oral carcinogenesis model in hamster. 0.5% 9, 10-dimethyl-1, 2-benzanthracene(DMBA) in mineral oil was topically applied to the buccal pouch of 75 hamster three times a week during the experimental periods. The experimental animals were subdivided into two groups of control and experiment. Only the mineral oil was applied to the control group. 0.5% DMBA in mineral oil was applied to the experimental groups of 6, 8, 10, 12, 14, 16, 18 and 20 weeks. The expression of the $TGF-{\alpha}$ and $TGF-{\beta}$ protein were evaluated by the distribution and intensity of positive cells during the carcinogenesis using the immunohistochemical study. The following results were obtained ; 1. The buccal pouch epithelium of hamster was histologically changed to the dysplasia at 6, 8, 10 weeks, carcinoma in situ at 12 weeks, and squamous cell carcinoma at 14 weeks. 2. The expression of the $TGF-{\alpha}$ was restricted to the parabasal and basal layers of the normal and dysplastic mucosa, but those positive cells were extended to the spinous layers of the epithelium in the carcinoma. 3. The degree of $TGF-{\alpha}$ expression was markedly decreased in the carcinoma at 16, 18, 20. The strong positive staining in the center of cancer islands and weak positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. 4. The positive index of the $TGF-{\alpha}$ had a tendency to increase with DMBA- applied time. There was a statistically significant difference between 12, 18, 20 experimental group and control group (p<0.05). 5. The expression of the $TGF-{\beta}$ was shown at the cytoplasm of all control and experimental groups, and the parabasal and basal layers of the normal and dyslastic mucosa, but it was shown at the basal layers of the epithelium in the carcinoma. 6. $TGF-{\beta}$ was expressed diffusely at 16, 18, 20 experimental group. The strong positive staining in the center of cancer islands and positive staining in periphery of tumor were seen at the stage of squamous cell carcinoma. From the above findings, the expression of $TGF-{\alpha}$ and ${\beta}$ in oral carcinogenesis model seems to have two formal stages, the first being an overexpression step as reaction to uncontrolled growth and the second being one in which external protein accumulate in the surrounding stroma and intracytoplasm. Overexpression of $TGF-{\alpha}$ and ${\beta}$ may have important cooperative roles for the promotion of cancer and factor of prognosis.

• BMB Reports
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• v.30 no.2
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• pp.119-124
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• 1997

Transforming growth $factor-{\beta}\;(TGF-{\beta})$ is a multifunctional polypeptide that exerts biological roles including cell proliferation, differentiation, extracellular matrix deposition and apoptosis in many different cell types. $TGF-{\beta}$, although known as a negative growth regulator, has not been tested in human embryo lung (HEll cells. This study attempts to understand the role of $TGF-{\beta}$ on growth control of HEL cells in relationship to tyrosine phosphorylation pattern of cellular proteins. In density-arrested HEL cells treated with $TGF-{\beta}$, analysis of Western immunoblot showed induction of tyrosine phosphorylation of two major cellular proteins (15 kDa and 45 kDa). In normal proliferating HEL cells with different concentrations of serum, further analysis indicated that the increase in tyrosine phosphorylation of a 45 kDa protein was regulated in serum concentration-dependent manner. However, in proliferating HEL cells treated with $TGF-{\beta}$, tyrosine phosphorylation of 45 kDa was down-regulated. Calcium involvement in the regulation of tyrosine phosphorylation of 45 kDa and 15 kDa proteins was also examined. Tyrosine phosphorylation of 15 kDa protein but not of 45 kDa protein was regulated by exogenous calcium. The level of tyrosine phosphorylation of 15 kDa protein was low at reduced caclium concentration and high at elevated caclium concentration. $TGF-{\beta}$ reversed the pattern of tyrosine phosphorylation of 15 kDa protein. These results suggest that tyrosine phosphorylation of 45 and 15 kDa proteins in HEL cells may be controlled depending on the physiological status of the cells, i.e., low in arrested cells and high in proliferating cells. And the tyrosine phosphorylation of the two proteins appears to be down- or up-regulated by $TGF-{\beta}$.