• Biomolecules & Therapeutics
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• 제19권2호
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• pp.187-194
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• 2011

Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

• Asian-Australasian Journal of Animal Sciences
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• 제16권7호
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• pp.1055-1059
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• 2003

Keratins, the constituents of epithelial intermediate filaments, are precisely regulated in a tissue and development specific manner. There are two types of keratin in bovine. The type I is acidic keratin and the type II is neutral/basic keratin. 1.5 kb of 5' flanking sequence of Korean cattle Keratin IV gene, type II keratin (59 kDa), was cloned and sequenced. A symmetrical motif AApuCCAAA are located in a defined region upstream of the TATA box. Proximal SP1, AP1, E-box and CACC elements as the major determinants of transcription are identified. When it was compared to the bovine sequence from -600 bp to ATG upstream, the homology was 97% in nucleotide sequence. Several A and T sequences, located in the promoter region, are deleted in the Korean cattle. An expression vector consisted of Korean cattle Keratin IV gene promoter/SV40 large T antigen was transfected to HaCaT cell (Epithelial keratinocyte). The transformed HaCaT cells showed active proliferation when treated with PDGF (Platelet-derived growth factor) in 0.3% soft agar compared to control cells. These results indicate that Korean cattle Keratin IVgene promoter can be used as a promoter for transfection into epithelial cell.

• Radiation Oncology Journal
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• 제22권1호
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• pp.40-54
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• 2004

목적 : 정상 흰쥐의 심장에 방사선을 조사한 군과 captopril과 방사선 조사를 병용한 군의 병리학적 소견과 $TNF-{\alpha}$ (tumor necrosis factor-alpha), $TGF-{\beta}1$ (transforming growth factor-beta), PDGF (platelet-derived growth factor), FGF (fibrobiast growth factor)-2의 발현상태를 비교 관찰함으로써 심장의 조기 방사선손상에서 captopril의 효과와 보호기전에서의 사이토카인의 역할을 알아보고자 하였다. 대상 및 방법 : 실험동물(Sprague-Dawley-Dawley 흰쥐)은 대조군, 방사선 조사 단독군, captopril과 방사선 조사 병용군으로 분류하였다. 방사선 조사 단독군은 12.5 Gy의 X-선을 좌흉곽에 단일 조사하였다. Captopril과 방사선 조사 병용군은 1일 50 mg/kg의 captopril을 방사선조사 1주 전부터 실험종료 시인 8주 후까지 식수에 섞어 음용시켰다. 실험 결과는 방사선조사 2주와 8주 후에 심방과 심실의 병리조직 소견을 비교 관찰하였고 면역조직화학염색으로 $TNF-{\alpha}$, $TGF-{\beta}$1, PDGF, FGG-2의 발현을 관찰하였다. 결과 : 방사선조사 2주 후 병리조직 소견상 대조군에 비해 심한 심방 심장막(pericardium) 섬유소 침착(p=0.093), 심실 혈관주위(perivascular space) 부종(p=0.082)과 혈관주위 및 사이질(interstitium)의 섬유소 침착(p=0.018)이 보였으며, 심방 심장막의 섬유소 침착은 심실에 비해 현저하였다(p=0.009). 방사선 조사 후 8주의 변화는 2주 소견에 비해서 부종 및 섬유소 침착은 소멸되었고, 섬유화가 관찰되었는데 이는 심실보다 심방의 심장막에서 현저하게 나타났다. Captopril과 방사선 병용군은 방사선에 의한 심장손상이 감소되어 병리학적 소견상 대조군과 비교 시 유의한 차이가 없었고, 방사선 조사 단독군과 비교하여 특히 2주 후에 심방의 심내막(endocardium) 섬유소 침착(p=0.047)과 심실의 사이질 섬유소 침착(p=0.019) 및 부종(p=0.042)이 현저히 감소되었다. 방사선조사 2주 후에 $TNF-{\alpha}$, $TGF-{\beta}$1, PDGF, FGF-2의 발현이 방사선 조사 단독군에서 대조군과 비교하여 증가되었으며, 특히 심방의 심장막 및 심장내막에서 현저하게 증가되었다. 방사선조사 8주 후에는 심장막의 $TNF-{\lapha}$, $TGF-{\beta}$1이 계속 증가되었으며 $TGF-{\beta}1$는 심방 심내막(p=0.015)과 사이질(p=0.025)에서 특히 증가되었으나, PDGF와 FGF-2는 감소되었다. Captopril과 방사선조사 병용군은 2주에 방사선 조사 단독군에 비하여 $TNF-{\alpha}$, $TGF-{\beta}$l, PDGF의 발현이 감소되었으며, 8주에는 심방과 심실의 심장막에서 $TNF-{\alpha}$가 현저히 감소되었고(p=0.049, p=0.009) $TGF-{\beta}1$, PDGF의 경우 감소되는 경향을 보였으나 유의한 차이는 없었다. 결론 : 흰쥐의 심장에 captopril을 방사선과 병용 투여하여 병리조직 소견을 관찰한 결과 방사선에 의한 조기 심장 손상이 감소됨을 확인할 수 있었다. 또한 방사선조사 후 2주 및 8주에 병용군에서 단독군에 비하여 $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF 등의 발현이 감소하는 양상이 관찰되어, captopril이 사이토카인의 발현을 억제함으로써 방사선에 의한 심장손상을 감소시킬 수 있을 것으로 생각된다.

• Archives of Plastic Surgery
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• 제40권5호
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• pp.530-535
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• 2013

Background Platelet-rich plasma (PRP) has more concentrated platelets than normal plasma (approximately 150-400${\times}10^3$ cell/dL). Platelets excrete several growth factors and cytokines that are associated with the healing and regeneration process. However, even though PRP is widely used, the mechanism or actual effect is presently unclear. Therefore, this study was performed to investigate the levels of growth factors and platelet concentration rate. Methods Autologous blood for preparing PRP was obtained from healthy subjects aged 25 to 35 years. The samples were divided into 4 experimental groups (inactivated whole blood, inactivated PRP, activated whole blood with thrombin and calcium chloride, and activated PRP). The platelet counts in the blood were analyzed and the growth factors were quantitatively measured. A statistical analysis was performed by using Dunn's multiple comparison test. Results In the blood cell analysis, the platelet count of the PRP group was approximately 4.25 times higher than that of the whole blood group. In the quantitative analysis of growth factors, the platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor-${\beta}$ of the inactivated and activated PRP groups were higher than those of the inactivated and activated whole blood groups (P<0.05). Conclusions In this study, the platelet count and the levels of PDGF-AB and PDGF-BB in the PRP were determined. Further, more research is required on the bioactivity level of the growth factors secreted during the process of PRP preparation and the potency of growth factors that can be exerted physiologically in vivo.

• 약학회지
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• 제41권4호
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• pp.433-438
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• 1997

MT 51005 as a potent inhibitor of phospholipase C(PLC) was purified from the culture broth of a fungal strain No. 51005 isolated from soil. It was identified as a benzaldehyde d erivative, anguillosporal. by the physico-chemical properties and spectroscopic data. Anguillosporal showed the inhibitory activity against purified PLC with an $IC_{50}\;of\;13{\mu}g/ml$. And it also inhibited the formation of inositol phosphates($IP_t$) in platelet-derived growth factor(PDGF)-stimulated $NIH3T3{\gamma}1$ cells with an $IC_{50}\;of\;0.8{\mu}g/ml$.