• International Journal of Oral Biology
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• 제30권3호
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• pp.99-103
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• 2005

Bone morphogenetic proteins (BMPs), members of a large group of TGF-beta family, are important molecular regulators of morphogenesis of numerous tissues and organs, including bones and teeth. Most BMPs are capable of inducing bone formation in vivo and therefore are of considerable clinical interest for regenerating mineralized tissues. Recently, we have developed a method to culture cells from human cementum (human cementum-derived cells, HCDCs). HCDCs, when attached to synthetic hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic and transplanted into immunodeficient mice, formed histologically identifiable cementum-like tissue. Since it is unclear to what extent BMPs are involved in cementogenesis, the aim of this study was to establish which BMPs are expressed by cementogenic HCDCs and whether the expression of BMPs is related to the degree of cellular differentiation in vitro. HCDCs were maintained in growth medium (DMEM/F12 supplemented with 10% FBS) until confluent (proliferation stage). Upon reaching confluence, cells were incubated in the differentiation medium (DMEM/F12 medium containing 10% FBS and 50 mg/ml ascorbic acid) for 14 days (differentiation stage). Next, HCDCs were incubated in mineralization medium (DMEM/F12, 50 mg/ml ascorbic acid, 2.5 mg/ml of ITS (insulin-transferrinselenium), 5 mM beta-glycerophosphate and $10^{-8}M$ dexamethasone) for another 14 days (mineralization stage). At the end of each differentiation stage, total RNA was isolated and evaluated for BMPs (2 through 8) expression by employing real time RT-PCR. HCDCs expressed most of BMPs examined except BMP-7 and BMP-8. Furthermore, on average, the highest levels of BMPs were expressed at the earlier differentiation stage, prior to the initiation of mineralization in vitro. These results indicate that several BMPs are expressed during cementoblastic differentiation and suggest that BMPs may be involved in the homeostasis of human cementum.

• Korean Journal of Acupuncture
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• 제31권4호
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• pp.168-178
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• 2014

Objectives : Mahuang-Chuanwu(Mahwang-Cheonoh) Pharmacopuncture(MCP) has been used to treat obesity in Clinical Korean Medicine. MCP solution(MCPS) is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and lipogenesis. Methods : In the present study, we examined the effects of MCPS on differentiation and lipogenesis of 3T3-L1 adipocytes. To elucidate the mechanism of the effects of MCPS on lowering lipid content in 3T3-L1 adipocytes, we examined whether MCPS modulates the expressions of transcription factors to induce lipogenesis and adipogenic genes related to regulate the accumulation of lipids. Results : Our results showed that MCPS significantly inhibited differentiation and lipogenesis of 3T3-L1 adipocytes in a dose-dependent manner. MCPS suppressed the mRNA expressions of cytidine-cytidine-adenosine-adenosine-thymidine(CCAAT)/enhancer binding proteins ${\alpha}$($C/EBP{\alpha}$), C/EBP ${\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$) genes related to the induction of adipose differentiation. MCPS inhibited the mRNA expressions of adipose-specific aP2, adipsin, lipoprotein lipase(LPL), CD36, TGF-${\beta}$, and leptin genes related to the fat formation. MCPS downregulated the mRNA expressions of liver X receptor(LXR) ${\alpha}$ and fatty acid synthase(FAS) genes related to the induction of lipogenesis. In addition, MCPS reduced the production of adipocyte-induced pro-inflammatory cytokines. Conclusions : MCPS could regulate the accumulation of lipids and expression of adipogenic genes via inhibition of transcript factors related to induction of adipose differentiation.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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• pp.153-158
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• 2007

Background: Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis. We examined the effect of oral administration of the antioxidant mixture ("L-Skin Care") on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanisms of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancing of pro collagen synthesis in mouse dorsal skin. Methods: Female SKH-l hairless mice were orally administrated "L-Skin Care" (test group) or vehicle (control group) for 10 weeks with UVB irradiation by three times a week. The intensity of irradiation was gradually increased from 30 to $180mJ/cm^2$. Microtopographic and histological assessments of the dorsal skins were carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation. Results: Our "L-Skin Care" significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis and hyperkeratosis. Oral administration of "L-Skin Care" significantly prevented UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinases and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-$\beta$ (TGF-$\beta$) expression. Conclusion: Oral administration of "L-Skin Care" significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied with enhancement of collagen synthesis.

• Molecules and Cells
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• 제42권4호
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• pp.321-332
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• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• BMB Reports
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• 제42권9호
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• pp.617-622
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• 2009

We investigated the genetic associations of ischemic stroke by identifying epistasis of its heterogeneous subtypes such as small vessel occlusion (SVO) and large artery atherosclerosis (LAA). Epistasis was analyzed with 24 genes in 207 controls and 271 patients (SVO = 110, LAA = 95) using multifactor dimensionality reduction and entropy decomposition. The multifactor dimensionality reduction analysis with any of 1- to 4-locus models showed no significant association with LAA (P > 0.05). The analysis of SVO, however, revealed a significant association in the best 3-locus model with P10L of TGF-$\beta{1}$, C1013T of SPP1, and R485K of F5 (testing balanced accuracy = 63.17%, P < 0.05). Subsequent entropy analysis also revealed that such heterogeneity was present and quite a large entropy was estimated among the 3 loci for SVO (5.43%), but only a relatively small entropy was estimated for LAA (1.81%). This suggests that the synergistic epistasis model might contribute specifically to the pathogenetsis of SVO, which implies a different etiopathogenesis of the ischemic stroke subtypes.

• 한국수산과학회지
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• 제42권2호
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• pp.139-145
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• 2009

We cloned and sequenced the open reading frame (ORF) cDNA encoding myostatin from the muscle of abalone (Haliotis discus hannai). The ORF cDNA of the abalone myostatin is 1134 bp and encoded 377 amino acid residues that were 60-96% homologous with the amino acids of other organism myostatins. In addition, the ORF contained a conserved proteolytic cleavage site (RXRR) and nine conserved cysteine residues in the C-terminus. Semi-quantitative RT-PCR revealed the presence of myostatin mRNA in various tissues. The strongest expression was observed in the mantle of female abalone, and the gills and heart of male abalone.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6803-6812
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• 2015

Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu, $TGF{\beta}$, and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation.

• Childhood Kidney Diseases
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• 제21권1호
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• pp.1-7
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• 2017

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and $TGF-{\beta}1$ expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

• BMB Reports
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• 제48권12호
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• pp.645-646
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• 2015

The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.244-251
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• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.