• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권3호
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• pp.205-217
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• 2005

Distraction osteogenesis is a technique of lengthening bone including soft tissue by gradual separation of surgically divided bone surfaces. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the molecular mechanisms governing the formation of new bone in distracted bone segments remain largely unclear. However, such information has significant clinical implications because it may enable targeted therapeutic manipulations designed to accelerate osseous regeneration. The purpose of this study was to evaluate the expression of TGF-$\beta$1, IGF-I and bFGF in distraction osteogenesis according to different distraction rates in a rabbit's mandible. When twenty-four adult rabbits underwent open osteotomy between the premolar and mental foramen, an external bilateral distraction device was applied. Latency was allowed for five days before distraction. Three different distraction rates were 0.7 mm/day (A, n=8), 1.4 mm/day (B, n=8) and 2.4 mm/day (C, n=8). The distraction device was activated with the same distraction rhythms of twice a day until 4.9 mm (A & B group) and 8.4 mm (C group) length gains was achieved. The animals were sacrificed at postoperative 3, 7, 14 and 28 days. The bony specimens were stained with H&E for histologic examination, and RT-PCR analysis was done for the identification of the expression of TGF-$\beta$1, IGF-I and bFGF. The results obtained from this study were as follows : The 0.7 mm/day and 1.4 mm/day distraction rate groups were shown to improve regenerative bone formation on radiographic and histologic examination. Also, TGF-$\beta$1, IGF-I and bFGF expression increased in the 0.7 mm/day and 1.4 mm/day distraction rate groups. But the 2.4 mm/day distraction rate group specimen was different with adjacent normal bone and hardly expressed of growth factors. These findings suggest that improved new bone formation in the 0.7 mm/day and 1.4 mm/day distraction rates is associated with enhanced expression of TGF-$\beta$1, IGF-I and bFGF by mechanical tension stress. Additionally, the 0.7 mm/day and 1.4 mm/day distraction rate groups were significantly different from the 2.4 mm/day distraction rate group in the expression of growth factors. According to the above results, it seems possible to apply a distraction rate of up to 1.4 mm/day a day in rabbit's mandible. And further studies are needed to evaluate growth factors of TGF-$\beta$1 and IGF-I, which are excellent in expression.

• Tuberculosis and Respiratory Diseases
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• 제70권5호
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• pp.405-415
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• 2011

Background: In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-${\beta}1$ in a human pleural mesothelial cell line, MeT-5A. Methods: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-${\beta}1$ for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. Results: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-${\beta}1$ increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. Conclusion: TGF-${\beta}1$ is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-${\beta}1$ stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.

• 대한의생명과학회지
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• 제13권3호
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• pp.213-221
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins, c-erbB-2 oncoprotein and $TGF-{\beta}1$ and tumor prognostic factors in colon cancer including the tumor size, histological differentiation and Dukes' stage. The expression rate of p53 protein was 11.4% (4 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation. In other words, the poorer differentiation, the higher the expression rate of p53 protein (P<0.05). The expression rate of p21 protein was 17.1% (6 cases) at well differentiation, 40.0% (14 cases) at moderately differentiation, and 8.6% (3 cases) at poorly differentiation, indicating that, as the histological malignant degeneration progressed, the expression rate of p21 protein decreased distinctively (P<0.05). However, the correlation of the above mentioned proteins with tumor size and Dukes' stage was not recognized. The expression rate of c-cerbB-2 oncoprotein was 11.4% (4 cases) at well differentiation, 54.3% (19 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation, indicating that the poorer differentiation, the higher expression rate of c-erbB-2 oncoprotein (P<0.05). The expression rate of $TGF-{\beta}1$ was 17.1% (6 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 11.4% (4 cases) at poorly differentiation. As Dukes' stage progressed, the expression rate of $TGF-{\beta}1$ was 8.6% (3 cases) in stage A, 20.0% (7 cases) in stage B, 37.1 % (13 cases) in stage C, and 11.4% (4 cases) in stage D. There was a difference in expression rates between Dukes' stages (P<0.05). In 10 cases, p53 protein was positive while p21 protein was negative, and in 6 cases, p53 protein was negative whereas p21 was positive (P<0.05). Therefore, a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed. In conclusion, since there was a signigicant correlation between histological differentiation of colon cancer and the expressions of p53 and p21 proteins and c-erbB-2 oncoprotein, and between Dukes' stage and the expression of $TGF-{\beta}1$, it was conformed that the overexpression of p53 and p21 proteins, c-erbB-2 oncoprotein, and $TGF-{\beta}1$ is closely associated with the occurrence of colon cancer and its progress. Accordingly, this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권4호
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• pp.405-411
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• 2008

Purpose : Cyclosporine A (CsA) is a versatile immunosuppresive agent used to prevent graft rejection syndrome and treat autoimmune disease. One of the major side effects associated with CsA is the abnormal gingival hyperplasia. The purpose of this study was to investigate the relationship between the mRNA expression of the MMP-1, TIMP-1, and $TGF-{\beta}_1$ and the concentration of CsA in cultured human gingival keratinocytes. Materials & Methods : Gingival keratocytes were obtained from gingival tissues of 4 healthy donors. The cultured gingival keratocytes were incubated with increasing concentrations of CsA (0-2000 ng/ml) for 24 hours and the expression of MMP-1, TIMP-1, and $TGF-{\beta}_1$ were determined by reverse transcription-polymerase chain reaction (RT-PCR). Results : The expressions of MMP-1 and $TGF-{\beta}_1$ were not significantly different according to the concentrations of CsA. The expression of TIMP-1 was significantly increased at the CsA concentration of 500 ng/ml. Conclusion : We concluded that the gingival hyperplasia induced by CsA was more related with TIMP-1 than MMP-1 or $TGF-{\beta}_1$ on gingival collagen metabolism in patients treated with CsA.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.136-148
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• 2002

본 연구는 osteoblastic cells에서 estogen 의 생합성을 유도하는 aromatase의 activity에 대한 봉독(蜂毒)작용을 측정하여, 봉독치료시 Arthritis의 진행 억제 및 estogen의 의한 bone formation의 효과여부를 검증하기 위해 실행하였다. 사용된 세포주로는 Osteoblastic phenotype으로 분화가 유도되는 Human leukaemic cell line FLG 29.1 및 the primary first-passage osteoblastic cells (hOB cells)이며, 이들을 각각 배양하고 각각의 RNA를 isolation한 뒤 PCR 증폭을 하였다. Aromatase에 대한 활성인자인 TPA와 TGF-${\beta}1$ 및 봉독을 이용하여 aromatase의 expression 및 activity에 대해 미치는 영향을 측정한 바, aromatase expression은 FLG 29.1 cell와 hoB cells에서, 50nM TPA 24시간 처리, 봉독 2 ~ 4시간 처리와 TGF-${\beta}1$ 3시간 처리로 유도한 결과 TPA와 TGF-${\beta}1$의 경우는 서로 유사하였고, 봉독에서 상대적으로 높게 나타났다. Aromatase activity는 FLG 29.1 cell, hoB cells에서 24시간 incubation한 결과, 모든 실험에서 일정하게 선상증가를 보였다. $5{\mu}{\ell}/m{\ell}$ BV에서 TPA와 TGF-${\beta}1$보다 뚜렷하게 증가하였으며, 0.5mM Bt2-cAMP, 50nM dexametasone처리에서는 유의성이 없었다. Estrogen 생합성을 촉매하는 aromatase activity BV가 처리에서 현저하게 증가하였기에, Rheumatis arthritis의 bone destruction에 대해 BV가 효과적인 역할을 할 것으로 보여진다.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2001년도 전기 제11차 학술대회 논문집
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• pp.50-51
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• 2001

In ultrastructure study of testis, Sertoli cells start to differentiate at 16 days of gestation. Transcripts of FSH receptor, IGF-I receptor, ER $\alphareceptor, $ $TGF-\beta$ receptor and androgen receptor were highly and initially expressed at 16 day of gestation. As results of in situ PCR at 16 day of gestation, transcripts of FSH, IGF-I receptor were detected in Sertoli cells and spermatogonia, whereas the receptors of $ER\alpha, $ $TGF-\beta$ and androgen were detected in Sertoli cells. Therefore, expression of FSH and estrogen $\alpha, $ androgen, IGF-I and $TGF-\alpha$ could play an important role during fetal and prepubertal testicular development by stage specific manner in mouse.

• Fisheries and Aquatic Sciences
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• 제10권1호
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• pp.16-23
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• 2007

Myostatin (GDF8) is a growth factor that limits muscle tissue growth and development in vertebrates. We isolated a myostatin-like gene (Py-MSTN) from the marine invertebrate, the scallop Patinopecten yessoensis. Py-MSTN was highly expressed in the adductor muscle and in the gill unexpectedly. Amino acid analysis showed that Py-MSTN has 49% amino acid sequence identity and 64% similarity to human myostatin (Hs-MSTN), and 42% identity and 61% similarity to myoglianin, the only invertebrate homolog. These results indicated that Py-MSTN may be functionally similar to the vertebrate MSTN than the invertebrate homolog. Phylogenetic analysis suggested that Py-MSTN is an ancestral form of vertebrate MSTN and GDF11 and does not belong to other $TGF-{\beta}$ family members. Molecular modeling showed that Py-MSTN exhibits a similar tertiary structure to mammalian BMP7, a member of $TGF-{\beta}$ family. In addition, the amino acid residues which contact extracellular domain of the receptor were relavively conserved. Given these results, we propose that Py-MSTN is a functionally active member of the $TGF-{\beta}$ family and is involved In muscle growth and regulation.

• Molecules and Cells
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• 제19권3호
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• pp.445-451
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• 2005

Activation-induced cytidine deaminase (AID) is needed for Ig class switch recombination (CSR). We explored the effect of LPS on the expression of AID during B cell differentiation, and the role of AID in IgA isotype expression. In normal spleen B cells, LPS increased AID transcription up to 48 h post-stimulation, i.e. around the time of Ig CSR. TGF-${\beta}1$ and AID were required for IgA expression, and LPS contributed to $TGF{\beta}1$-induced IgA production largely by inducing AID. Interestingly, LPS repressed AID transcription in $sIgA^+$ B cells but still stimulated IgA production mainly by increasing the rate of IgA secretion. Our data indicate that LPS contributes to $TGF{\beta}1$-induced IgA isotype expression in at least two ways: by stimulating AID transcription before CSR and by enhancing the IgA secretion rate after CSR.

• Journal of Korean Biological Nursing Science
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• 제8권2호
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• pp.41-59
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• 2006

Chronic liver diseases and hepatic cancer have been reported as 10% of cause of death in Koreans. Regardless of various causes, chronic liver disease accompanies commonly hepatic fibrosis. But still the mechanism of hepatic fibrosis remains poorly understood. Using the dimethylnitrosamine(DMN)-induced hepatic fibrosis rat model, We performed to evaluate the possible therapeutic effect of RIP(extracts of Phellodendron amurense and Patrinia scabiosaefolia) and to investigate the changes in referential connective tissue proteins($TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin, and vimentin) as a marker of fibrogenesis. For these purposes, liver tissues were stained with H & E, and Azan staining for estimation of developing fibrosis. In the DMN-treated rat liver tissue, fibrosis were developed forming incomplete septal fibrosis. Whereas, in the RIP-treated rat liver tissues, the fibrosis were decreased recovering to normal morphology. The expressions of $TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin($\alpha-SMA$), and vimetin were increased in the DMN-treated rat liver tissues, but decreased in the various areas of RIP-treated rat liver tissues. According to these results, RIP could be a possible therapeutic agent to reduce hepatic fibrosis, and the $TGF-{\beta}_1$, ${\alpha}$-SMA, and vimentin could be possible indicative markers of hepatic fibrosis development and recovery.

• The Korean Journal of Physiology and Pharmacology
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• 제9권3호
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• pp.159-164
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• 2005

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) ${\beta}1$ and laminin ${\beta}1$ was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF ${\beta}1$ mRNA and protein, which was ameliorated by NAC. Although the expression of laminin ${\beta}1$ mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF ${\beta}1$.