• International Journal of Industrial Entomology and Biomaterials
• /
• v.27 no.1
• /
• pp.159-165
• /
• 2013

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF-${\beta}$) superfamily and are involved in osteoblastic differentiation. The largest TGF-${\beta}$ superfamily subgroup shares genetic homology with human BMPs (hBMPs) and silkworm decapentaplegic (dpp). In addition, hBMPs are functionally interchangeable with Drosophila dpp. Bombyx mori dpp may induce bone formation in mammalian cells. To test this hypothesis, we synthesized the 1,285-base pairs cDNA of full-length B. mori dpp using total RNAs obtained from the fat body of 3-day-old of the $5^{th}$ instar larvae and cloned the cDNA into the pCEP4 mammalian expression vector. Next, B. mori dpp was expressed in C3H10T1/2 cells. The target cells transfected with the pCEP4-Bm dpp plasmid showed biological functions similar to those of osteogenic differentiation induction growth factors such as hBMPs. We determined the relative mRNA expression rates of Runt-related transcription factor 2 (RUNX2), osterix, osteocalcin, and alkaline phosphatase (ALP) to validate the osteoblast-specific differentiation effects of B. mori dpp by performing quantitative real-time RT-PCR. Interestingly, mRNA expression levels of the 3 marker genes except RUNX2, in cells expressing B. mori dpp were much higher than those in control cells and C3H10T1/2 cells transfected with pCEP4. These results suggested that B. mori dpp signaling regulates osterix expression during osteogenic differentiation via RUNX2-independent mechanisms.

• Archives of Plastic Surgery
• /
• v.42 no.6
• /
• pp.686-694
• /
• 2015

Background Rosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice. Methods Sixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta ($250{\mu}g$) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test. Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-${\beta}1$ expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA. Conclusions Rose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.3
• /
• pp.305-314
• /
• 2016

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

• Journal of Korean Neurosurgical Society
• /
• v.53 no.4
• /
• pp.207-212
• /
• 2013

Objective : Recent studies have shown encouraging progress toward the use of autogenic and allogenic mesenchymal stem cells (MSCs) to arrest, or even lead to partial regeneration in, intervertebral disc (IVD) degeneration. However, this technology is still in its infancy, and further development is required. The aim of this study was to analyze whether rat adipose-derived mesenchymal stem cells (ADMSC) can differentiate towards IVD-like cells after treatment with transforming growth factor ${\beta}3$ (TGF-${\beta}3$) in vitro. We also performed quantitative analysis of gene expression for ADMSC only, ADMSCs treated with TGF-${\beta}3$, and co-cultured ADMSCs treated with TGF-${\beta}3$. Methods : ADMSCs were sub-cultured to homogeneity and used in fluorocytometry assays for CD11, CD45, and CD90/Thy1. ADMSCs were differentiated in spheroid culture towards the chondrogenic lineage by the presence of TGF-${\beta}3$, dexamethasone, and ascorbate. We also co-cultured pure ADMSCs and nucleus pulposus cells in 24-well plates, and performed immunohistochemical staining, western blotting, and RT-PCR for quantitative analysis of gene expression. Results : Results of fluorocytometry were positive for CD90/Thy1 and negative for CD11 and CD45. TGF-${\beta}3$-mediated induction of ADMSCs led to the expression of the differentiation markers of intervertebral disc-like cells, such as aggrecan, collagen II, and sox-9. Co-cultured ADMSCs treated with TGF-${\beta}3$ showed higher expression of differentiation markers and greater extracellular matrix production compared with ADMSCs treated with TGF-${\beta}3$ alone. Conclusion : ADMSC treated with TGF-${\beta}3$ may be an attractive source for regeneration therapy in degenerative IVD. These findings may also help elucidate the pathologic mechanism of MSC therapy in the degeneration of IVD in vivo.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8725-8734
• /
• 2014

The transforming growth factor-${\beta}1$ (TGF-${\beta}1$) gene 29 T/C polymorphism is thought to be associated with breast cancer risk. However, reports are largely conflicting and underpowered. We therefore conducted a meta-analysis of all available case-control studies relating the TGF-${\beta}1$ 29T/C polymorphism to the risk of developing breast cancer by including a total of 31 articles involving 24,021 cases and 31,820 controls. Pooled ORs were generated for the allele contrasts, with additive genetic, dominant genetic and recessive genetic models. Subgroup analysis was also performed by ethnicity for the TGF-${\beta}1$ 29T/C polymorphism. No association was found in the overall analysis (C vs T: OR=1.028, 95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR= 1.022, 95% CI=0.963-1.085, p-value 0.478; CC vs TT: OR= 1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+ TC: OR= 1.031, 95% CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR= 0.945, 95% CI=0.827-1.080, p-value 0.403). Similarly, in the subgroup analysis by ethnicity, no association was found in Caucasian (C vs T: OR= 1.041, 95% CI=0.932-1.162, p-value 0.475; CC vs TC: OR= 1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR= 1.081, 95% CI=0.865-1.351, p-value 0.493; CC vs TT+TC: OR= 1.047, 95% CI=0.929-1.180, p-value 0.453; TT vs CC+TC: OR= 0.929, 95% CI=0.775-1.114, p-value 0.429;) and Asian populations (C vs T: OR= 1.004, 95% CI=0.908-1.111, p-value 0.931; CC vs TC: OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR= 1.015, 95% CI=0.848-1.214, p-value 0.871; CC vs TT+TC: OR= 1.000, 95% CI=0.909-1.101, p-value 0.994; TT vs CC+TC: OR= 0.967, 95% CI=0.808-1.159, p-value 0.720;). No evidence of publication bias was detected during the analysis. No significant association with breast cancer risk was demonstrated overall or on subgroup (Caucasian and Asian) analysis. It can be concluded that TGF-${\beta}1$ 29T/C polymorphism does not play a role in breast cancer susceptibility in overall or ethnicity-specific manner.

• Preventive Nutrition and Food Science
• /
• v.19 no.3
• /
• pp.136-144
• /
• 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-${\beta}1$] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-${\beta}1$ expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression.

• IMMUNE NETWORK
• /
• v.5 no.4
• /
• pp.215-220
• /
• 2005

Background: Transforming growth factor-${\beta}$ (TGF-${\beta}1$) directs class switch recombination (CSR) to IgA isotype, which is a predominant antibody in mucosal surfaces. Although IgA is preferentially committed in mucosal lymphoid tissues, it is not definitely established whether hallmarks of IgA CSR such as IgA germ-line transcripts (GLT ${\alpha}$), post-switch transcripts (PST ${\alpha}$) and circle transcripts (CT ${\alpha}$) are readily expressed in such tissues. Therefore, we compared the expression of these transcripts among mouse Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen. Methods: Levels of GLTs, PSTs and CTs were measured by RT-PCR in isolated PPs, MLNs and spleen cells. Results: GLT ${\alpha}$ and PST ${\alpha}$ were well expressed in PP and MLN cells but in spleen cells. Similar patterns were observed in the expression of GL ${\gamma}$2b and PST ${\gamma}$2b. On the other hand, these transcripts were only inducible in spleen cells upon stimulated with LPS and TGF-${\beta}1$. In addition, CT${\alpha}$ and CT${\gamma}$2b were detected in PP cells. Conclusion: PP B cells readily express IgA GLT, PST, and CT. Overall expression patterns of these transcripts were similar in MLN cells. Thus, these results suggest that microenvironment of PP and MLN influences spontaneous IgA CSR, which lacks in systemic lymphoid tissues such as spleen.

• Microbiology and Biotechnology Letters
• /
• v.50 no.4
• /
• pp.533-547
• /
• 2022

This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.

• Reproductive and Developmental Biology
• /
• v.33 no.3
• /
• pp.163-169
• /
• 2009

Many biological systems are regulated by an intricate set of feedback loops that oscillate with a circadian rhythm of roughly 24 h. This circadian clock mediates an increase in body temperature, heart rate, blood pressure, and cortisol secretion early in the day. Recent studies have shown changes in the amplitude of the circadian clock in the hearts and livers of streptozotocin (STZ)-treated rats. It is therefore important to examine the relationships between circadian clock genes and growth factors and their effects on diabetic phenomena in animal models as well as in human patients. In this study, we sought to determine whether diurnal variation in organ development and the regulation of metabolism, including growth and development during the juvenile period in rats, exists as a mechanism for anticipating and responding to the environment. Also, we examined the relationship between changes in growth factor expression in the liver and clock-controlled protein synthesis and turnover, which are important in cellular growth. Specifically, we assessed the expression patterns of several clock genes, including Per1, Per2, Clock, Bmal1, Cry1 and Cry2 and growth factors such as insulin-like growth factor (IGF)-1 and -2 and transforming growth factor (TGF)-${\beta}1$ in rats with STZ-induced diabetes. Growth factor and clock gene expression in the liver at 1 week post-induction was clearly increased compared to the level in control rats. In contrast, the expression patterns of the genes were similar to those observed after 5 weeks in the STZ-treated rats. The increase in gene expression is likely a compensatory change in response to the obstruction of insulin function during the initial phase of induction. However, as the period of induction was extended, the expression of the compensatory genes decreased to the control level. This is likely the result of decreased insulin secretion due to the destruction of beta cells in the pancreas by STZ.

• Journal of Life Science
• /
• v.28 no.1
• /
• pp.37-42
• /
• 2018

Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.