• BMB Reports
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• 제46권2호
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• pp.107-112
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• 2013

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II $TGF{\beta}$ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional $TGF{\beta}$ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제40권5호
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• pp.240-245
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• 2014

Angiokeratoma is a benign cutaneous lesion of the capillaries, presenting as dilated vessels in the upper part of the dermis. Although this disorder is classified into various types and has been occasionally reported in the skin of the scrotum or extremities, the involvement of the oral cavity mucosa has been rarely reported. The present study reports a case of angiokeratoma circumscriptum in the buccal mucosa. The expression of vascular endothelial growth factor (VEGF) and both of its receptors (VEGFR-1 and VEGFR-2) was demonstrated by immunohistochemistry in the endothelial cells lining the dilated vessels. The expression of VEGFR-2 was higher than that of VEGFR-1 in the endothelial cells in the lesion, indicating an increased rate of endothelial cell proliferation within the lesion. Interestingly, some of the endothelial cells co-expressed VEGF and its two receptors. These results suggest that endothelial cells in the pathologically dilated vessels possess VEGF autocrine growth activity involved in vasculogenesis and maintenance in angiokeratoma lesions. To our knowledge, this is the second report published on isolated oral angiokeratoma confined to the buccal mucosa and the first case report on angiokeratoma circumscriptum involving the buccal mucosa.

• 대한약침학회지
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• 제23권2호
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• pp.54-61
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• 2020

Inflammation is an immune response of the human body but excessive inflammation is taken as a major factor in the development of many diseases including autoimmune disorders, cancer and nerve disorders etc. In this regards the need is to suppress the inflammatory response. Suppression of extra or imperfect inflammatory response is not a big deal provided there is an exact knowledge of particular target in the body. Recent advancements in Pharmacological aspect made the therapy with improved outcomes in number of patients. Anticytokine therapy might be one of the important and novel approaches for inflammation and Arthritis. This can be achieved only when we go through the pathophysiology of expression and identification of mediators. Let's take an example of cytokine like interleukins (IL), chemokines, interferons (INF), tumor necrosis factors (TNF-α), growth factors, and colony stimulating factors) release pathway which is a major signalling protein in inflammatory response. In the present study we have reviewed the recent pharmacological therapeutic advancement, inflammatory mediators, receptors, and major signalling pathways. Such information will not only provide the idea about the mechanism of action of Pharmaceuticals and molecular targets but also it provides a new aspect for drug designing and new corrective approaches in existing clinical medicines. This study will be a source of good information for the researchers working in the area of drug designing and molecular Pharmacology especially in anti-inflammatory and anti arthritic medicines for target based therapy.

• 생명과학회지
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• 제12권2호
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• pp.164-172
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• 2002

유방암세포는 여러 종류의 성장인자 수용체를 가지며, 이를 통해 성장신호를 전달한다. 따라서, 이러한 수용체들의 신호전달 경로에 있는 공통적인 2차전달자들의 조절기작을 밝히는 것이 중요하다. 이 연구는 MCF-7 cell에 있어서, 에스트로젠과 TGF-$\alpha$ , EGF와 같은 성장인자의 mitogenic signal을 전달하는 second messenger에 폴리아민이 어떤 영향을 미치는지, 또 membrane-associated proteins의 인산화에 폴리아민이 어떤 조절기작을 가지는지를 알아보고자 한다. 폴리아민 생합성 억제제인 DFMO는 154, 134, 116, 104 kDa의 membrane-associated proteins의 인산화를 억제하였고, DFMO에 의해 억제된 단백질 인산화는 폴리아민 첨가로 다시 회복 되었다. $E_2$, TGF-$\alpha$, EGF, DFMO는 모두 단백질의 타이로신 인산화에는 크게 영향을 미치지 않았으나, 처리해준 폴리아민에 의해 154, 134, 116 kDa의 단백질의 타이로신 인산화는 급격히 증가하였다. 또한 $E_2$, TGF-$\alpha$, EGF는 모두 같은 단백질에서 유사하게 인산화를 유도하였다. 이러한 결과로 볼 때, $E_2$와 TGF-$\alpha$, EGF와 같은 성장촉진인자의 signaling pathway는 154, 134, 116, 104 kDa 단백질을 기질로 하는 여러 가지 다양한 종류의 protein kinase를 통해서 서로 cross-talk하고 있으며, 폴리아민은 154, 134, 116, 104 kDa와 같은 여러 가지 membrane-associated proteins의 인산화를 조절함으로서 이러한 cross-talk pathway에 관여하고 있는 것으로 사려된다.

• 대한방사성의약품학회지
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• 제4권2호
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• pp.106-114
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• 2018

Angiogenesis is the new blood vessel formation process and has known to a fundamental event of tumor growth and metastasis. Especially, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the crucial regulators of angiogenesis in tumor. VEGF-A is one of the VEGF family and binds to endothelial cell specific VEGFR1 and VEGFR2, which are associated with tumor growth and tumor angiogenesis. $VEGF_{121}$ is more tumorigenic isomer of VEGF-A. Targeted VEGF or VEGFR molecular imaging has been widely used to enable diagnosis and monitoring of proliferation and development of angiogenic tumors. Therefore, in this review, we have focused on the radioligands with $VEGF_{121}$ for angiogenesis of tumor.

• 한국영양학회:학술대회논문집
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• 한국영양학회 1995년도 추계학술대회 초록
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.127-130
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• 2002

The present study was aimed to investigate whether the adriamycin-induced nephrosis is associated with an altered regulation of local renin-angiotensin system (RAS) in the kidney. Rats were subjected to a single injection of adriamycin (2 mg/kg body weight, IV) and kept for 6 weeks to allow the development of nephrosis. They were then divided into two groups, and supplied with and without cilazapril, an angiotensin converting enzyme (ACE) inhibitor, in drinking water (100 mg/l) for additional 6 weeks. Another group without adriamycin-treatment served as control. The mRNA expression of renin, ACE, type 1 and type 2 angiotensin II receptors (AT1R, AT2R), and transforming growth factor $(TGF)-{\beta}1$ was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. Adriamycin treatment resulted in heavy proteinuria. Accordingly, the mRNA expression of renin, ACE, and AT1R was increased in the renal cortex, while that of AT2R was decreased. Co-treatment with cilazapril attenuated the degree of proteinuria. While not affecting the altered expression of renin, cilazapril decreased the expression of ACE to the control level. Cilazapril further increased the expression of AT1R, while it restored the decreased expression of AT2R. The expression of $(TGF)-{\beta}1$ was increased by the treatment with adriamycin, which was abolished by cilazapril. An altered expression of local RAS components may be causally related with the development of adriamycin-induced nephrosis, in which AT1R is for and AT2R is against the development of nephrosis.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.69-69
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• 2003

Although effect of TGF$\beta$$_1$ on preimplantation embryo development was reported at mice, little information relevant to this subject is known in bovine. The objectives of this study were to investigate TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors type I and II expression, known as important factors in the embryo development, at unfertilized oocytes and fertilized embryos that will be used as basic data to be compared to NT embryos. We postulated that TGF$\beta$$_1$ may have a beneficial effect on the preimplantation embryo and show different expression patterns as embryo stages change. We have used immunocytochemistry to investigate the presence in unfertilized oocytes and preimplantation embryos of TGF$\beta$$_1$ and the essential components of the TGF$\beta$$_1$ signalling pathway, TGF$\beta$$_1$ receptors type I and II. We found that both receptors, as well as TGF$\beta$$_1$, were present in the unfertilized oocytes. This indicates that TGF$\beta$$_1$, is a maternally expressed protein. At the morulae and blastocyst stages the TGF$\beta$$_1$ receptor type II was not present, but the TGF$\beta$$_1$ receptor type I was present at both stages and we can confirm the TGF$\beta$$_1$ expression of high level at 8-cell stage. These findings support our hypothesis that the TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors may interact with the oocyte and preimplantation embryo, and that TGF$\beta$$_1$ signalling may be important for the development of the oocyte and the preimplahtation embryo.

• Journal of Korean Neurosurgical Society
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• 제52권1호
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• pp.7-13
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• 2012

Objective : The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). Methods : A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Results : Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). Conclusion : The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).