• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2005년도 Proceedings of The 2nd Asian Society of Veterinary Pathology Symposium(Vol.2) and 2005 Annual Meeting of The Korean Society of Veterinary Pathology(Vol.9)
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• pp.103.1-104
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• 2005

• Journal of Cancer Prevention
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• 제23권4호
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• pp.162-169
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• 2018

$TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

• Journal of Microbiology and Biotechnology
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• 제26권6호
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• pp.1063-1066
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• 2016

Longan (Dimocarpus longan Lour.) has been used as a traditional oriental medicine and possesses a number of physiological activities. In this study, we used cell-based herbal extract screening to identify longan fruit extract (LFE) as an activator of osteoblast differentiation. LFE up-regulated alkaline phosphatase (ALP) activity, induced mineralization, and activated Runx2 gene expression in MC3T3-E1 cells. Furthermore, treatment of MC3T3-E1 cells with LFE promoted the phosphorylation of extracellular signal-regulated kinase1/2 (Erk1/2); however, abrogation of Erk1/2 activation with PD98059 resulted in down-regulation of the phospho-SMAD1/5/8 and Runx2 levels, which in turn reduced the ALP activity. Our findings suggest that LFE exerts its osteogenic activity through activation of the ERK signaling pathway and may have potential as an herbal therapeutic or a preventive agent for the treatment of osteoporosis.

• Tuberculosis and Respiratory Diseases
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• 제79권3호
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.

• Nutrition Research and Practice
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• 제11권3호
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• pp.190-197
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• 2017

BACKGROUND/OBJECTIVES: Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. MATERIALS/METHODS: The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis. We investigated the inhibitory effect of melanin on the osteoclasts formation through tartrate-resistant acid phosphatase (TRAP) activity and TRAP stains in Raw 264.7 cell. RESULTS: The melanin extract of GD was not cytotoxic to MG-63 cells at concentrations of $50-250{\mu}g/mL$. Alkaline phosphatase (ALP) activity and bone mineralization of melanin extract-treated cells increased in a dose-dependent manner from 50 to $250{\mu}g/mL$ and were 149% and 129% at $250{\mu}g/mL$ concentration, respectively (P < 0.05). The levels of BMP-2, osteocalcin, and COL-1 gene expression were significantly upregulated by 1.72-, 4.44-, and 2.12-fold in melanin-treated cells than in the control cells (P < 0.05). The levels of RUNX2 and SMAD5 proteins were higher in melanin-treated cells than in control vehicle-treated cells. The melanin extract attenuated the formation of receptor activator of nuclear factor kappa-B ligand-induced TRAP-positive multinucleated RAW 264.7 cells by 22%, and was 77% cytotoxic to RAW 264.7 macrophages at a concentration of $500{\mu}g/mL$. CONCLUSIONS: This study provides evidence that the melanin extract promoted osteoblast differentiation by activating BMP/SMADs/RUNX2 signaling and regulating transcription of osteogenic genes such as ALP, type I collagen, and osteocalcin. These results suggest that the effective osteoblastic differentiation induced by melanin extract from GD makes it potentially useful in maintaining bone health.

• Restorative Dentistry and Endodontics
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• 제35권3호
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• pp.152-163
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• 2010

이 연구에서는 mineral trioxide aggregate (MTA)를 in vitro로 인간치수세포에 적용하였을 때 유전자들의 변화를 조사하였다. 실험군은 MTA를 teflon tube (직경 10 mm 길이 2 mm)에 담아 4시간 경화시킨 후HDPCs에 적용하였고, 대조군은 빈tube만을 적용하였다. 6, 24, 72시간 후 total RNA를 추출하여 microarray를 이용하여 분석하여, 2배 이상 또는 절반 이하의 변화를 보이는 유전자 중 선택적으로 역전사 중합효소 연쇄반응(reverse transcriptase polymerase chain reaction)을 사용하여 발현을 확인하였다. 24,546개의 유전자 중에서 109개의 유전자가 2배 이상 up-regulation되었으며(예. FOSB, THBS1, BHLHB2, EDN1,IL11, FN1, COL10A1, TUFT1) 69개의 유전자가 50%이하로 down-regulation되었다(예. SMAD6, DCN). MTA는 bio-inert한 재료라기 보다는 치수세포에 다양한 경로로 영향을 주는 재료로 사료된다. 특히 치수세포의 분화와 증식에 관여하는 유전자의 변화에 영향을 주며 석회화 과정에 관여하는 유전자의 변화에 직접적인 영향을 주리라 사료된다.

• 대한화장품학회지
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• 제48권2호
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• pp.157-167
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• 2022

본 연구에서는 7 개의 아미노산으로 이루어진 헵타펩타이드의 섬유아세포 활성 증가 및 광노화 조건에서의 세포 손상 억제 효과를 확인하였다. 실험 결과 헵타펩타이드 처리 시 섬유아세포 증식 및 세포외기질(extracellular matrix, ECM) 구성 인자의 발현이 증가되었다. 그리고 자외선 A (ultraviolet A, UVA) 조사에 의해 유도된 광노화조건에서 감소된 세포 생존율이 헵타펩타이드에 의해 증가되었고, UVA 조사에 의해 유도된 세포 사멸, 기질금속단백질분해효소-1(matrix metalloproteinases-1, MMP-1) 발현 및 세포 내 활성산소종(reactive oxygen species, ROS) 수준이 헵타펩타이드에 의해 감소되었다. UVA 조사 시 나타나는 transforming growth factor-β (TGF-β)/smad 기전 억제와 그에 따른 ECM 구성 인자 발현 감소 또한 헵타펩타이드에 의해 회복되었다. 또 다른 광노화 유도 조건으로 heat shock을 주었고 헵타펩타이드를 전 처리 하였을 때 heat shock에 의한 mitogen-activated protein kinase (MAPK) 인산화 및 MMP-1 발현이 억제됨을 확인할 수 있었다. 이 결과를 종합해 볼 때, 본 연구의 헵타펩타이드는 섬유아세포의 활성을 촉진하며, 광노화 유도 모델로 사용된 UVA 조사 및 heat shock 조건에서도 세포 내 ROS 억제 효과를 보여 세포 손상에 대한 회복 및 보호 효과를 나타내는 것으로 보인다. 이러한 진피 보호 효과를 갖는 헵타펩타이드는 향 후 신규 화장품 소재로 응용될 수 있을 것으로 기대된다.

• Journal of Nutrition and Health
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• 제56권6호
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• pp.602-614
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• 2023

본 연구는 근생성 및 근위축 완화효능을 가진 유효소재 발굴의 필요성에 의해 polygalacin D가 근원세포 분화 및 미토콘드리아에 미치는 영향과 항암제 유도 근위축에 대한 완화효과를 각각 세포 및 동물실험을 통해 확인하고자 하였다. 그 결과, polygalacin D는 다핵을 지닌 근관세포의 수와 분화 종결인자인 MHC isoforms의 발현량을 증가시켰고 근육 내 단백질 분해 인자인 MuRF1, Smad2/3의 발현량은 유의적으로 감소시켰다. 또한 미토콘드리아 생합성 조절인자인 Pgc1α의 발현은 증가시키고 미토콘드리아 분열인자인 Drp1과 Fis1의 발현은 감소시켰다. 한편 zebrafish 동물모델을 통해 항암제 유도 근위축에 대한 개선효과를 확인한 결과, polygalacin D는 항암제에 의해 유도된 근위축과 미토콘드리아 손상을 완화시켰다. 이상의 결과들은 polygalacin D가 미토콘드리아 기능 증진을 매개로 근원세포 분화 촉진 및 근육 단백질 분해 저하 효과를 지닐 뿐만 아니라, 미토콘드리아 손상을 개선하여 항암제로 유도된 근위축에 대한 완화 효과를 나타냄을 시사한다. 따라서 본 연구를 통해 polygalacin D가 근생성 및 근위축 예방과 치료를 위한 잠재적인 유효소재로서의 가능성을 제시하였다.

• Journal of Periodontal and Implant Science
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• 제36권3호
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• pp.627-637
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• 2006

이 연구는 rh BMP-7-immobilized substrates에 대한 백서 태자 두개관 세포의 반응을 석회화 결절 측정, 알카리 효소 분석, 역전사 중합반응 및 단백질 분석등으로 평가하여 다음과 같은 결과를 얻었다. 1. 배양 14일 째, 석회화 결절 형성율을 측정한 결과, rh BMP-7-immobilized substrates에서 대조군과 비교하여 더 많은 석회화 결절을 형성하였다. 2. 배양 7일에 염기성 인산 분해효소 활성도는 rh BMP-7-immobilized substrates에서 대조군에 비해 효소 활성도가 유의하게 높았다. 3. 역전사 중합반응의 결과에서 BSP 와 OCN 유전자 발현은 대조군보다 더 현저하였다. 4. 단백질 분석에서 rh BMP-7-immobilized substrates와 대조군 모두 Smad 1,5,8 단백질의 인산화를 활성화시키지 못했다. 이상의 결과 rh BMP-7-immobilized substrates는 백서 태자 두개관세포가 조골세포로의 분화와 석회화를 유도하며 따라서 rh BMP-7-immobilized substrates는 임프란트 주변의 골 형성에 유용하리라 사료된다.

• Molecules and Cells
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• 제22권3호
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• pp.291-299
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• 2006

Vitexin, a natural flavonoid compound identified as apigenin-8-C-${\beta}$-D-glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory properties. In this study, we investigated its effect on hypoxiainducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human hepatoma (HepG2) cells. Vitexin inhibited HIF-$1{\alpha}$ in PC12 cells, but not in HOS or HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A, enolase 1, and collagen type III in the PC12 cells. We found that vitexin inhibited the migration of PC12 cells as well as their invasion rates, and it also inhibited tube formation by human umbilical vein endothelium cells (HUVECs). Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N-terminal kinase (JNK), but not of extracellular-signal regulated protein kinase (ERK), implying that it acts in part via the JNK pathway. Overall, these results suggest the potential use of vitexin as a treatment for diseases such as cancer.