• 생약학회지
• /
• 제44권2호
• /
• pp.110-117
• /
• 2013

Cirsium japonicum (CJ) leaf (L) alcoholic extracts were investigated for analysis their active components (flavonoids and flavanolignans; silymarins) and inhibitory effect on transforming growth factor (TGF)-${\beta}$ induced hepatic stellate cells (HSCs, LX-2 cells) activation. The CJ root (R) extracts were also analyzed and compared with leaf extracts. Total flavonoid and polyphenol contents of the leaf extracts showed higher than those of the root extracts. The content of each flavonoid compound, which was analyzed by HPLC, in CJ-L extracts was also higher than in CJ-R extracts. The results of flavanolignans content in CJ-L and CJ-R extracts were consistent in flavonoid and polyphenol. We studied inhibitory effect of two extracts against TGF-${\beta}1$ induced HSCs activation. The CJ-L extracts significantly suppressed overexpression of profibrogenic factor, ${\alpha}$-smooth muscle actin and collagen-${\alpha}1$(I). The CJ-R extract also showed inhibitory effect on TGF-${\beta}1$ induced HSCs activation, but the efficacy was lower than in CJ-L extract. These results suggest that CJ-L may contribute to the fibrotic liver treatment.

• International Journal of Industrial Entomology and Biomaterials
• /
• 제5권2호
• /
• pp.201-204
• /
• 2002

This study was undertaken to find effects of ethanol extracts from Bombyx mori on the hyperglycemia induced by streptozotocin in rats. Blood glucose level of rats increased depending on experimental days after streptozotocin treatment. But there was no difference in blood glucose level between the rats injected with ethanol extracts of B. mori and normal rats. There was no significant difference in the kidney fibrosis between the rats injected with ethanol extrscts of B. mori and normal rats at all ages examined. The transforming growth factor-$\beta$l ($TGF-{\beta}1$) protein was detected in the glomerulay endothelial cells and tubular epithelial cells of streptozotocin rats at 14 days of age. In the rats injected with ethanol extracts of B. mori to the kidneys, the $TGF-{\beta}1$ protein was detected very faintly. The $TGF-{\beta}1$ mRNA of streptozotocin rats increased at 14 days of age, and this was higher than the rats injected with ethanol extrscts of B. mori. Taken these together, the results suggest that the ethanol extracts of B. mori ameliorate hyperglycemia of the rats induced by streptozotocin.

• 한국동물번식학회:학술대회논문집
• /
• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
• /
• pp.94-94
• /
• 2003

Endocrine disrupters (EDs) are exogenous chemicals that interfere with the production, releasing, metabolism, excretion, binding of natural hormones, and whole endocrine systems. EDs are very dangerous since they are extremely stable, not easily degraded, and accumulated in fat and tissue. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is known as the most toxic EDs. Therefore, this study was conducted to investigate the effects of TCDD on proliferation of human breast cancer (MCF-7) and endometrial adenocarcinoma (Hec-1B) cells. 10, 100, and 1000 nM of TCDD were treated with steroid free condition. Viable cell counting, MTT, and BrdU assay was performed to investigate cell proliferation. Apoptosis was investigated using DNA laddering. Although, DNA fragmentation as the evidence of apoptosis was not detected, all of these cell lines showed restricted proliferation at 48 hrs after 100 and 1000 nM TCDD treatments. Recently, it has been reported that the expression of transforming growth factor $\beta$s (TGF-$\beta$s) are increased in TCDD treatment and also involved in regulation of cell cycle. Therefore, these results were considered that the decreased cell prolifcration by TCDD is related to the expression of TGF-$\beta$s.

• 대한임상검사과학회지
• /
• 제50권3호
• /
• pp.304-312
• /
• 2018

본 연구에서는 면역 억제 역할을 하는 것으로 알려져 있는 조절 T 세포 (regulatory T cell, Treg)의 새로운 생리학적 기능 대하여 확인해보고자 하였다. 시험관내나 동물실험에서 조절 T 세포가 분비하는 transforming growth factor ${\beta}1$ ($TGF-{\beta}1$)에 의하여 이식 직전까지 췌장섬세포의 생존률을 향상시키면서 동시에 혈당조절 기능이 향상될 수 있을 것이라는 가설이다. 이를 증명하기 위하여 마우스를 이용한 1형 당뇨병 모델을 제작한 뒤, 180 IEQ (islet equivalents)의 췌장섬세포를 동종간 이식하였다. 췌장섬세포는 이식 수술 시행 전까지 48시간 동안 $4{\times}10^6$의 Treg 세포와 함께 배양하여 Treg 유래 $TGF-{\beta}1$에 충분히 노출시킨 뒤 사용하였다. Treg 단독군, 췌장섬세포 단독군 및 Treg/islet 동시 배양군에서 각각 $TGF-{\beta}1$, IL-6 및 인슐린 분비 수준의 변화를 측정하였다. Treg/islet 동시 배양군에서 IL-6와 인슐린 분비는 증가하였고 (P<0.0005, P<0.005), 췌장섬세포 단독군과 비교하여 생존율이 향상되었다(P<0.005). 또한, 이식 후, 동시 배양된 췌장섬세포는 1형 당뇨병 마우스 모델에서 혈당 수치를 보다 효율적으로 조절하였다. 이러한 결과는 Treg 세포가 $TGF-{\beta}1$ 분비를 통하여 췌장섬세포의 기능과 생존력을 향상시킬 수 있음을 시사한다.

• Molecules and Cells
• /
• 제25권1호
• /
• pp.105-111
• /
• 2008

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.

• 대한한의학회지
• /
• 제30권6호
• /
• pp.35-43
• /
• 2009

Objectives: Hwangryunhaedok-tang (HRHDT), a prescription composed of four herbs, has been wi dely used in Oriental Medicine for the treatment of cerebral infarction. However, the mechanisms by which the herbal formula affects on the production of pro- and anti-inflammatory cytokines in cerebral infarction patients remain unknown yet. Methods: The levels of pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6, IL-10, and TGF-${\beta}1$ were determined in peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients under our experimental conditions. Results: The secretory levels of pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6, and IL-10 were significantly increased in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. However, pretreatment with HRHDT significantly inhibited the secretion of pro- and anti-inflammatory in PBMCs. Also, HRHDT induced a significant increase of transforming growth factor (TGF)-b1 in PBMCs. Conclusions: These data indicate that HRHDT may be beneficial in the suppression of inflammatory processes of cerebral infarct through suppression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, and IL-10 and induction of TGF-${\beta}1$.

• Biomolecules & Therapeutics
• /
• 제24권2호
• /
• pp.132-139
• /
• 2016

The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.

• The Korean Journal of Physiology and Pharmacology
• /
• 제14권6호
• /
• pp.385-390
• /
• 2010

Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-${\beta}1$, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with $1\;{\mu}M$ phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-${\beta}1$. PAl-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-${\beta}1$ significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-${\beta}1$-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.

• Archives of Plastic Surgery
• /
• 제33권1호
• /
• pp.1-4
• /
• 2006

Cryopreserved fibroblast implants represent a major advancement for healing of chronic wounds. Bone marrow stromal cells, which include the mesenchymal stem cells, have a low immunity-assisted rejection and are capable of expanding profoundly in a culture media. Therefore, they have several advantages over fibroblasts in clinical use. The ultimate goal of this study was to compare the wound healing accelerating growth factor secretion of the bone marrow stromal cells with that of the fibroblasts and this pilot study particularly focuses on the growth factor secretion to accelerate wound healing. Bone marrow stromal cells and fibroblasts were isolated from the same patients and grown in culture. At 1, 3, and 5 days post-incubating, secretion of basic fibroblast growth factor(bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta(TGF-${\beta}$) were compared. In TGF-${\beta}$ secretion fibroblasts showed 12~21% superior results than bone marrow stromal cells. In contrast, bFGF levels in the bone marrow stromal cells were 47~89% greater than that in fibroblasts. The VEGF levels of the bone marrow stromal cells was 7~12 fold greater than that of the fibroblasts. Our results suggest that the bone marrow stromal cells have great potential for wound healing accelerating growth factor secretion.

• Asian-Australasian Journal of Animal Sciences
• /
• 제18권5호
• /
• pp.716-722
• /
• 2005

Carcass weight and backfat thickness are primary yield grading factors. Insulin-like growth factor (IGF)-I/-II, transforming growth factor $\beta$1 (TGF-$\beta$1), and epidermal growth factor (EGF) regulate the proliferation and differentiation of cells including adipocytes. Also, interleukin (IL)-2/-6, cortisol, and dehydroepiandrosterone-sulfate (DHEA-S) are known to be related to muscle growth and fat depth. However, the relationships between endocrine factors and carcass grade have not been studied. Therefore, this study aimed to measure the concentrations of endocrine factors in serum and muscle, and to investigate the relationship of endocrine factors with carcass grade. A total of 60 crossbred gilts (Duroc${\times}$Yorkshire${\times}$Landrace) were used. Blood from the jugular vein was collected at antemortem (7 days before slaughter) and postmortem periods, and M. Longissimus was collected at 45 min and 24 h after slaughter. The concentrations of IGF-I/-II, EGF, TGF-$\beta$1, IL-2/-6, cortisol and DHEA-S were analyzed by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). In general, IGF and EGF concentrations in serum and muscle of grade A carcasses were found to be higher than those of grade C carcasses at antemortem and postmortem periods, whereas the pattern of TGF-$\beta$1 concentration was reversed. In particular, the concentrations of muscle IGF-I (24 h postmortem) and serum TGF-$\beta$1 (antemortem) were significantly different between grades A and C (p<0.05). The present results indicate that serum and muscle growth factors affect carcass weight and backfat thickness, and indirectly suggest the possibility that carcass grade could be predicted by expression of serum and/or muscle growth factors.