• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8581-8586
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• 2014

Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-${\beta}$) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.

• BMB Reports
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• 제50권6호
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• pp.308-317
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• 2017

Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth $factor-{\beta}$ ($TGF-{\beta}$) superfamily receptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids, and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD proteins-mediated signal transduction leading to the expression of target genes implicated in the development or differentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with several clinical disorders, including representative pulmonary arterial hypertension, cancers, and metabolic diseases, thus demonstrating the physiological importance of BMPR2. In this mini review, we summarize recent findings regarding the molecular basis of BMPR2 functions in BMP signaling, and the versatile roles of BMPR2. In addition, various aspects of experimentally validated pathogenic mutations of BMPR2 and the linked human diseases will also be discussed, which are important in clinical settings for diagnostics and treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3527-3531
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• 2016

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

• IMMUNE NETWORK
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• 제6권3호
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• pp.145-153
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• 2006

Background: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. Methods: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. Results: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. Conclusion: In two different colon cancer cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher agspecific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.

• IMMUNE NETWORK
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• 제8권3호
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• pp.90-97
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• 2008

Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

• Journal of Acupuncture Research
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• 제20권1호
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• pp.159-176
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• 2003

Objective : The purpose of this study is to investigate the antioxidant activities of Alismatis Rhizoma herbal acupuncture by experimental methods. Methods : For this purpose, first, we put an emphasis in the control of enzymes of the antioxidant system in various changes inside the cell; these changes caused by the proliferation or the activation of the cell which were brought about by the handling of PMA and $TNF-{\alpha}$ into the THP-1 monocyte cell of the body each other. After that, we caused the acute oxidant symptom by the injection of AAPH into the mouse' abdominal cavity, and then applied the herbal acupuncture on S36 point(足三里), and finally, we measured the change of blood ingredient and the resistance against the activated oxygen of the red blood cell membrane, MDA, SOD, and catalase. Results : In vitro the revelation of $IL-1{\beta}$, IL-8, $TNF-{\alpha}$, NOS II and IL-6 were decreased and the revelation of IL-10, $TGF-{\beta}$, GM-CSFIL-12, GM-CSF and SOD were increased. The DNA-binding of $NF-{\kappa}B$ and AP-1 were activated and the formation of ROS in the THP-1 cell line was decreased. In vivo $IL-1{\beta}$ among producing the cytokine inside the plasma was meaningfully dwindled and the $INF-{\gamma}$ was meaningfully increased. The resistance of red blood cell membrane against the activated oxygen was meaningfully increased and the MDA formation was meaningfully dwindled, In the activation of hepatic antioxidase, the SOD was meaningfully increased. Conclusion : Alismatis Rhizoma herbal acupuncture by experimental methods has effected on the antioxidant activities.

• 대한본초학회지
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• 제31권4호
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• pp.71-77
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• 2016

Objectives : Adipogenesis was defined as a differentiation process of preadipocytes into the adipocytes. Thus, to control of this process can be one of the most important strategies to prevent obesity. Korean ginseng(Panax ginseng C.A. Meyer) is one of the most widely used medicinal herbs. Although multiple biological activities of Korean ginseng, particularly ginsenosides, have been known, the anti-adipogenic role and function of polysaccharides from Korean ginseng are still unclear. In this study, we examined anti-adipogenic activity of polysaccharides and its molecular basis mechanisms are further investigated.Methods : The cytotoxicity of KGP in 3T3-L1 was evaluated by MTT assay. Anti-adipogenic effect of KGP was examined by Oil Red O (ORO) staining and microscopy observation in 3T3-L1 mature adipocytes. The mRNA expression levels of adipogenic transcriptional factors were analyzed by reverse transcription-polymer chain reaction (RT-PCR). To elucidate the adipogenic molecular mechanism of KGT, SB431542 (TGF-β specific inhibitor) was used.Results : We found that polysaccharides showed no effect on the viability of 3T3-L1 preadipocytes. Dose dependent inhibitory effect of polysaccharides on 3T3-L1 adipogenesis was observed as judged by ORO staining and microscopic image analysis. To obtain further mechanistic insight into anti-adipogenic function of polysaccharides, we then tested the effect of polysaccharides treatment on the adipogenic marker genes. The mRNA expressions level of C/EBPα, PPARγ, C/EBPβ, and fatty acid synthase (FAS) were dose-dependently inhibited by KGP treatment in 3T3-L1 mature adipocytes.Conclusions : In conclusion, these findings suggest that the KGP could be used in treatment of obesity and overweight related diseases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권3호
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• pp.247-255
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• 2007

The bone morphogenic protein(BMP) can promote migration and growth of mesenchymal cells and initiate process for bone and cartilage formation. Cartilage-derived morphogenic protein(CDMP)-1 and -2 belong to the bone morphogenetic protein family in the transforming growth factor(TGF)-${\beta}$ superfamily. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation with biomolecular studies. The mechanism of pathogenesis in cartilaginous formation is still controversy. We examined the expression and localization of CDMP-1 and -2, in comparison with the localization of cartilaginous matrix proteins, in human normal salivary glands and 20 cases of pleomorphic adenoma using immunohistochemical methods. The results were followed. 1. CMP-1 was immunolocalized in the striated ducts and the intercalated ducts, but not expressed in excretory duct, CDMP-2 was not expressed in the normal salivary glands. 2. CMP-1 was immunolocalized in the ductal cell and cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor in any elements of the pleomorphic adenomas. 3. In transmission electron microscopic view, the tumor cells are composed of modifed myoepithelial cells between hyaline and myxoid stroma. 4. In Immuno-blot analysis, strong overexpression of CDMP-1 was frequently seen in pleomorphic adenomas, but the level of CDMP-2 was expressed minimally in pleomorphic adenoma. From the these results, it should be suggested that undifferentiated neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma, but not CDMP-2.

• BMB Reports
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• 제43권1호
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• pp.52-56
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• 2010

Silk fibroin, produced by the silkworm Bombyx mori, has been widely studied as a scaffold in tissue engineering. Although it has been shown to be slowly biodegradable, cellular responses to degraded silk fibroin fragments are largely unknown. In this study, silk fibroin was added to MG-63 cell cultures, and changes in gene expression in the MG-63 cells were screened by DNA microarray analysis. Genes showing a significant (2-fold) change were selected and their expression changes confirmed by quantitative RT-PCR and western blotting. DNA microarray results showed that alkaline phosphatase (ALP), collagen type-I alpha-1, fibronectin, and transforming growth factor-${\beta}1$ expressions significantly increased. The effect of degraded silk fibroin on osteoblastogenic gene expression was confirmed by observing up-regulation of ALP activity in MG-63 cells. The finding that small fragments of silk fibroin are able to increase the expression of osteoblastogenic genes suggests that controlled degradation of silk fibroin might accelerate new bone formation.

• BMB Reports
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• 제43권12호
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• pp.789-794
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• 2010

A novel gene, designated mgt-6, containing four splicing variants, was isolated from a gene trap clone library of C3H/10T1/2 cells transfected with retroviral promoterless gene-trap vector, ROSAFARY. The transcript variants were differentially expressed in murine tissues and cell lines and differentially responded to diverse stimuli including TGF-${\beta}1$ and mitogen-activated protein kinase (MAPK) inhibitors. The mgt-6 gene encoded a protein of 37 or 11 amino acid residuals with cytoplasmic distribution. However, when C3H/10T1/2 cells were treated with 5-azacytidine, the protein translocated into cell nucleus as indicated by fused LacZ or C-terminally tagged EGFP. Our preliminary results suggest that further study on the role of mgt-6 gene in cell transformation and differentiation may be of significance.