• Biomolecules & Therapeutics
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• 제28권1호
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• 한국가축번식학회지
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• 제21권2호
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• pp.177-183
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• 1997

The present study examined the effects of epidermal growth factor(EGF) and transforming growth factor-$\alpha$(TGF-$\alpha$) on in vitro maturation of porcine follicular oocytes. Basic medium used TCM-HEPES, and oocytes cultured for 42 hours in vitro. The results obtained are as follows; 1. The nuclear maturation rates of EGF-treated groups(10ng/ml, 75.9% ; 30ng/ml, 69.2% ; 50ng/ml, 67.2% ; 100ng/ml, 71.0%) on the porcine oocytes cultured in medium without pFF in vitro were significantly(P<0.01) higher than those of non-treated group(57.1%). When the oocytes were cultured in media with 10%(v/v) pFF, the nuclear maturation rates of 30ng EGF/ml(77.1%) treated group were significantly(P<0.01) higher than those of non-(59.2%) and EGF-treated groups(10ng/ml, 65.4% ; 50ng/ml, 65.5% ; 100ng/ml, 70.4%). 2. The nuclear maturation rates of 30ng TGF-$\alpha$/ml treated group(71.9%) in media without pFF in vitro were significatnly(P<0.01) higher than those of non-(57.1%) and TGF-$\alpha$ treated groups(10ng/ml, 60.4% ; 50ng/ml, 65.4% ; 100ng/ml, 60.0%). When the oocytes were cultured in media with 10%(v/v) pFF, the nuclear maturation rates of 30 and 50ng TGF-$\alpha$/ml(77.4% and 79.6%) treated groups(10ng/ml, 64.2% ; 100ng/ml, 61.6%). 3. On the effect of EGF(30ng/ml) and/or TGF-$\alpha$(30ng/ml) treated groups in medium without pFF in vitro, the nuclear maturation rates indicated 57.3, 60.4, 75.9 and 79.7% in media with no EGF & TFG-$\alpha$, TGF-$\alpha$ only, EGF only nad EGF＋TGF-$\alpha$ treated groups, respectively. The nuclear maturation rates in medium with EGF only or EGF＋TGF-$\alpha$ were significantly(P<0.01) higher than those non- and TGF-$\alpha$ treated groups. When the oocytes were cultured in media with 10%(v/v) pFF, the nuclear maturation ratesof EGF＋TGF-$\alpha$ treated group(75.9%) were significantly(P<0.01) higher than those of non-(59.2%), TGF-$\alpha$ only (64.2%) and EGF only(69.4%) treated groups.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1994년도 한국생물과학협회 학술발표대회
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• pp.159.1-159
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• 1994

No Abstract, See Full Text

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.216.1-216.1
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• 2001

• 생물정신의학
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• 제12권2호
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• pp.143-150
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• 2005

목 적: 많은 연구에서 정신분열병에서 염증반응체계의 활성화와 사이토카인의 변화가 병태생리학적 및 원인적 역할을 하는 것으로 보고되어 왔으며, 여기에는 type 1 Thelper cell(Th1), type 2 T helper cell(Th2), type 3 T helper cell(Th3)의 조절 이상이 제시되고 있다. 본 연구에서는 정신분열병 환자에서 항정신병 약물 치료 전후로 Th1 사이토카인인 interleukin-12(IL-12), Th3 사이토카인인 transforming growth factor-${\beta}1$(TGF-${\beta}1$)의 혈장 농도를 측정하였다. 방 법: 23명의 정신분열병 환자군과 31명의 정상대조군에서 IL-12와 TGF-${\beta}1$ 농도를 측정하였고 정신분열병 환자군에서는 8주간 항정신병 약물로 치료 후 다시 IL-12와 TGF-${\beta}1$의 농도를 측정하였다. 또한 정신분열병 환자군에서 치료전과 8주간 치료 후, 2차례에 걸쳐 Brief psychiatric rating scale(BPRS)를 측정하였다. 결 과: 치료전 IL-12 농도와 TGF-${\beta}1$ 농도 모두 정상대조군보다 환자군에서 유의하게 높게 나타났다. 8주간의 치료 후 TGF-${\beta}1$ 농도는 유의하게 감소하여 정상대조군의 농도와 차이를 보이지 않게 된 반면, IL-12의 농도는 유의하지 않은 감소를 보였다. BPRS 점수의 변화 및 IL-12 및 TGF-${\beta}1$의 농도의 변화 사이에는 유의한 상관관계가 없었다. 결 론: 정신분열병의 병태생리학에 사이토카인의 이상이 관여할 수 있으며, TGF-${\beta}1$이 중요한 역할을 하는 것으로 생각된다.

• 생물정신의학
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• 제13권1호
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• pp.32-37
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• 2006

Background : Several studies have suggested that alterations of cytokine level could be related to the pathophysiology of bipolar disorder. In this study, we measured plasma level of Interleukin-12(IL-12), a pro-inflammatory cytokine and transforming growth factor-${\beta}$1(TGF-${\beta}$1), an anti-inflammatory cytokine before and after treatment in acute manic patients. Methods : The plasma concentrations of IL-12 and TGF-${\beta}$1 were measured using quantitative ELISA in 18 bipolar disorder patients and 25 normal controls at admission and 6 weeks later. The psychopathology was measured by Brief Psychiatric Rating Scale(BPRS) and Young Mania Rating Scale(YMRS). Results : IL-12 levels were significantly higher in bipolar manic patients than in controls before treatment. Following the 6-week treatment, the IL-12 level was decreased than before treatment, but sustained still higher level than normal control. TGF-${\beta}$1 level was not significant different between manic patients and normal controls before treatment, but was increased after treatment comparing with before treatment in bipolar patients. The ratio of IL-12 and TGF-${\beta}$1 was significantly decreased after treatment. Conclusion : Cytokine abnormalities in bipolar disorder might be involved in the pathophysiology of the illness. It is possible that TGF-${\beta}$1 plays an important role in the regulation of immunological imbalance in bipolar disorder.

• Journal of Chest Surgery
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• 제39권11호
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• pp.805-809
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• 2006

배경: Transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) 단백질의 과발현이 폐기포 조직의 형성에 관여할 수 있다는 연구 결과를 본 연구팀은 발표한 바 있다. 이와 관련하여 폐기포벽에서 발견되는 섬유화에 관계될 것으로 생각되는 Transforming growth factor-beta 1(TGF-${\beta}1$) ligand의 발현의 변화를 보기 위하여 자연기흉 환자에서 폐기포 절제슬로 획득한 폐 기포조직을 면역조직화학적 염색법으로 염색하여 관찰하려 하였다. 대상 및 방법: 36명의 자연기흉의 환자에서 비디오흉강경 폐기포절제술 시 획득된 폐기포조직을 획득하였다. 36명 환자 중 남자가 34명, 여자가 2명이었고 연령은 14세에서 38세였다. 획득된 폐기포조직을 면역조직화학적 염색방법으로 염색하였다. 결과: 36명 중 19예에서 TGF-${\beta}1$ 양성이었고 24예에서는 transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$)가 양성이었다. 19예의 TGF-${\beta}1$ 양성 예 중 15예에서 TGF-${\beta}1RII$에도 양성으로 관찰되었다. 이 같은 양성 변화는 폐기포조직과 정상 폐 조직과의 경계선에서 가장 강하게 관찰되었다. 결론: TGF-${\beta}1$의 과발현은 TGF-${\beta}1RII$ 발현의 변이 여부와 마찬가지로 폐기포벽의 섬유화를 초래하여 폐기포 형성에 영향을 미치는 것으로 생각되며 확실한 규명을 위하여 분자생물학적 및 기타 추가적인 연구가 더 필요할 것으로 생각된다.

• IMMUNE NETWORK
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• 제1권2호
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Laboraroty Animal Research
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• 제33권2호
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• pp.76-83
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• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• Clinical and Experimental Reproductive Medicine
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• 제48권2호
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• pp.124-131
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• 2021

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.