초기 임신 탈락막에서의 TGF - β1 , β2 의 발현 ; 기저탈락막과 주변탈락막에서의 비교

황정혜(Jung Hye Hwang),고승희(Seung Hee Koh),한동익(Dong Ik Han),정성로(Sung Ro Chung),박문일(Moon Il Park),황윤영(Youn Young Hwang),장세진(Se Jin Jang) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.6

N/A Objective: Implantation is a complex process between developing embryo and maternal endometrium, especially decidua. Decidua is a specialized endometrium during pregnancy and decidua basalis is the real implantation site infiltrated directly by trophoblast cells. The decidua parietalis lines the uterine cavity away from the implantation site, not real implantation site. TGF- β1 and TGF-β2 have known as multipotential cytokines and expression of TGF- p and TGF-/3. increased in decidua during pregnancy than secretory phase of endometrium. However, there is little known about their expression in decidua parietalis, compared with decidua basalis. The purpose of this study was to compare the expression of TGF-β1 and TGF-β2 in the decidua basalis and decidua parietalis during early pregnancy. Methods: The early pregnant 26 samples were obtained at hysterectomy, which underwent surgery for cervical carcinoma, ovarian cancer, etc. Immunohistochemical staining of TGF- β1 and TGF-β2 was performed and staining intensity was semiquantified by using HSCORE. Results: TGF-β1 was slight]y expressed in the decidua basalis and decidua parietalis and there were no differences among them. But the expressions of TGF-β2 of stroma and glandular cells were higher in the decidua basalis than parietalis (p < 0.005). And the expressions of TGF-β2 were stronger than that of TGF-β1 in the both decidua of ear]y pregnancy (p < 0.005). Conclusion: In decidua basalis, especially stromal cells, the expression of TGF-β2 was increased than in the decidua parietalis. This suggests that TGF-β2 may play an important role in decidua basalis that is directly invasion site by embryo and can be regulated by embryonic derived local factor. TGF- 2, compared with TGF- β1, was increased in both implantation site and suggest it may regulate implantation process during early pregnancy.

한국 폐경여성에서 transforming growth factor - β1 ( TGF - β1 ) 유전자의 T869C 다형성 및 골밀도의 연관성

김정구(Jung Gu Kim),김석현(Seok Hyun Kim),최영민(Young Min Choi),문신용(Shin Yong Moon),이진용(Jin Yong Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

N/A Objective : To investigate the relationship between the T869C polymorphism of transforming growth factor-β1 (TGF-β1) gene, serum TGF-β1 levels and bone mineral density (BMD) in postmenopausal Korean women. Methods : The T869C polymorphism of TGF-β1 gene was analyzed by allele specific polymerase chain reaction (PCR) and electrophoresis in 296 postmenopausal Korean women. Serum bone alkaline phosphatase (BAP), CrossLaps (CTX), and TGF-β1 were measured by immunoassay, and enzyme linked immunosorbent assay respectively. BMD at the lumbar spine and proximal femur was determined by dual energy X-ray absorptiometry. Results : The frequencies of the TT, TC, and CC genotypes of the T869C polymorphism were 3.3%, 93.7%, and 2.3%. There were no significant differences in BMD of the lumbar spine and proximal femur or serum BAP and CTX levels across the three TGF-β1 genotypes. No significant differences in the distribution of TGF-β1 genotypes and serum TGF-β1 levels among normal, osteopenic, and osteoporotic postmenopausal women were observed. There was no relationship between serum TGF-β1 levels and BMD at the lumbar spine and proximal femur. Conclusions: The T869C polymorphism of TGF-β1 gene is not associated with serum TGF-β1 levels and BMD in postmenopausal Korean women,

Ganglioside GM3 participates in the TGF-β1-induced epithelial-mesenchymal transition of human lens epithelial cells

( Seok Jo Kim ),( Tae Wook Chung ),( Hee Jung Choi ),( Choong Hwan Kwak ),( Kwon Ho Song ),( Seok Jong Suh ),( Kyung Min Kwon ),( Young Chae Chang ),( Young Guk Park ),( Hyeun Wook Chang ),( Kyoung So 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

TGF-β(transforming growth factor-β)-induced EMT (epithelial-mesenchymal transition) induces the proliferation and migration of the HLE (human lens epithelial) cells. Ganglioside GM3, simple sialic-acid-containing glycosphingolipids on mammalian cell membranes, regulated various pathological phenomena such as insulin resistance and tumour progression. However, the relationship between ganglioside GM3 and TGF-β-induced EMT in the HLE B-3 cells is poorly understood. In the present study we demonstrated that ganglioside GM3 was involved in TGF-β1-induced EMT in HLE B-3 cells. Our results indicated that the expression of ganglioside GM3 and GM3 synthase mRNA were significantly increased in TGF-β1-induced HLE B-3 cells. Reporter gene analysis also demonstrated that transcriptional activation of the GM3 synthase gene was regulated by Sp1 (specificity protein 1) in HLEB-3 cells upon TGF-β1 stimulation. Interestingly, the inhibition of ganglioside GM3 expression by d-PDMP [d-threo-1phenyl-2decanoylamino-3-morpholino-1-propanol] and GM3 synthase shRNA (short hairpin RNA) resulted significantly in the suppression of cell migration and EMT-related signaling in HLEβ-3 cells stimulated by TGF-β. Furthermore, exogenous treatment of ganglioside GM3 rescue the expression of EMT molecules and cell migration suppressed by the depletion of ganglioside GM3 in TGF-β1-induced HLE B-3 cells. We also found that ganglioside GM3 in TGF -β1-induced HLE B-3 cells. We also found that ganglioside GM3 interacted with TGFβRs (TFG-β receptors) in TGF-β1-induced HLE B-3 cells. Taken together, these results suggest that ganglioside GM3 induced by TGF-β1 regulates EMT by potential interaction with TGFβRs.

Collagenase로 유도한 가토의 슬관절염에서 TGF-β1과 키토산-TGF-β1 복합체의 영향

장의찬 ( Eui Chan Chang ),송광섭 ( Kwang Sup Song ),정호중 ( Ho Jung Jung ),박영욱 ( Young Uk Park ),김미경 ( Mi Kyung Kim ) 대한슬관절학회 2006 대한슬관절학회지 Vol.18 No.2

목적: Collagenase type II로 유도한 가토의 슬관절염에서 TGF-β1과 키토산-TGF-β1 복합체의 영향을 알아보고자 하였다. 대상 및 방법: 가토 15마리의 우측 슬관절에 Collagenase를 실험 1일 및 4일째 두 번 주입하여 관절염을 유발한 후 실험 10일째 TGF-β1 (15 ng/mL, 1 mL, 1군), 키토산-TGF-β1 복합체(Chitosan: 5.8 g/mL, TGF-β1: 15 ng/mL, 1 mL, 2군), PBS(1 mL, 3군)을 각각 5마리씩 같은 부위에 주입하여 1주 간격으로 슬관절의 염증 소견 및 절름거림의 정도를 관찰하였다. 실험 4주째 관절연골과 활액막 조직을 얻어 각 군간의 육안적(India ink), 조직학적 소견(H&E, Safranin-O)을 평가(Kikuchi 점수)하였다. 결과: 외양상 염증 소견은 collagenase를 주사 후 1주 후에 가장 심하였으며, 이후로 각 군간 의미있는 차이는 없었으며, 절름거림의 정도는 3군에서 심했다. 육안적 소견은 2군에서 우수하였으며, 이러한 차이는 조직학적 평가에서 더욱 뚜렷하였다(1군: 평균 14±2.7, 2군: 평균 10.3±1.2, 3군: 평균 20.3±3.7) (p<0.05). 결론: Collagenase로 유도한 가토의 슬관절염의 회복에 과정에서 TGF-β1 단독 사용보다 키토산-TGF-β1 복합체의 사용이 효과적인 것으로 생각된다. Purpose; To evaluate the effects of the chitosan-TGF-β1 conjugate and TGF-β1 on osteoarthritic rabbit cartilage induced by collagenase type II. Materials and Methods; Chemical arthritis was induced in right knee of 15 rabbits by injection of collagenase type II (4 mg/mL, 0.25 cc) twice at day 1 and 4, and then each 5 rabbits were treated by intra-articular injection of TGF-β1 (15 ng/mL, 1 mL, group I), chitosan-TGF-β1 conjugate (Chitosan: 5.8 g/mL, TGF-β1: 15 ng/mL, group II) and PBS (1 mL, group III) at 10 days later in the same knees. The appearance of the injected knee joints and lameness were observed weekly. The articular cartilage and synovium obtained at 4 weeks were analysed by gross findings (India ink), histological examinations (H&E, Safrainin O) and evaluation through the Kikuchi score. Result; The osteoarthritic sign about knee joints was the most severe at 1 weeks after the initiation of collagenase injections, but there wasere no difference of 3 groups in osteoarthritic sign and lameness was most severe in group 3. Group 2 showed the most superior results in gross findings using india ink and the these results were more prominent in the evaluation of histological scoring (average scores of each group I:14±2.7, II:10.3±1.2, III:20.3±3.7). Conclusion; These results might suggest that, in the rabbit osteoarthritic knee model induced by collagenase, Chitosan-TGF-β1 conjugate is more effective than only TGF-β1 in inhibiting cartilage degeneration.

정상 후두상피, 후두이형성증 및 후두암에서의 Transforming Growth Factor-β1 발현

진영완,이동엽,차창일,박상훈,홍남표,안회영 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.4

폐암종에서 TGF-βl과 TGF-β 수용체 I의 발현

안혜경,최영희,심정원,박영의,김한겸,최종상,한정호 대한병리학회 1998 Journal of Pathology and Translational Medicine Vol.32 No.1

신장이식에서의 TGF-β1 유전자형 분석

전동석 대한임상병리학회 2001 대한임상병리학회지 Vol.21 No.3

Tiul1 and TGIF are Involved in Downregulation of TGFβ1-induced IgA Isotype Expression

박경훈,남은희,서구영,서수련,김평현 대한면역학회 2009 Immune Network Vol.9 No.6

TGF-β1 is well known to induce Ig germ-line α (GLα) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-β signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFβ1-induced GLα promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLα promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFβ1- induced GLα expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced IgA secretion, but not GLTγ3 and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFβ1-induced IgA isotype expression. TGF-β1 is well known to induce Ig germ-line α (GLα) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-β signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFβ1-induced GLα promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLα promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFβ1- induced GLα expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced IgA secretion, but not GLTγ3 and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFβ1-induced IgA isotype expression.

심장판막에서 TGF-β1의 생성과 분포

고재기,김남균,김민호,채제건,고규영 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.7

자연발생 당뇨쥐의 신장에서 섬유화 초래인자인 Transforming Growth Factor-β1의 발현

김형엽 ( Hyung Yup Kim ),장재휘 ( Jae Hwi Jang ),한상미 ( Sang Mi Han ),안기성 ( Ki Sung Ahn ),박성배 ( Sung Bae Park ),김현철 ( Hyun Chul Kim ),박관규 ( Kwan Kyu Park ) 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.2

목적 : 당뇨병성 신질환은 당뇨병중에서 나타나는 합병증의 하나로서 사구체경화에 의한 신장의 기능상실로 이어진다. 이러한 당뇨병적 사구체경화와 과혈당증은 세포외기질의 증가로 인해 일어난다고 알려져 있으며, 그 중에 하나로 transforming growth factor (TGF)-β1의 과발현에 기인한다고 알려져 있다. 당뇨병에 의해 사구체의 경화가 일어나면 그 회복이 불가능하며 근본적인 치료법이 정립되어 있지 않기 때문에, TGF-β1의 발현시기와 위치를 찾는 것은 이를 바탕으로한 치료 시기 및 방법 결정에 크게 도움이 될 것이다. 방법 : 자연발생적인 제 2형 당뇨병 모델인 OLETF 쥐를 사용하였으며, 대조군으로는 유전적으로 유사하나 당뇨병이 발생하지 않는 LETO 쥐를 사용하여, 당뇨에 의한 사구체 섬유화와 TGF-β1의 발현양상을 비교 조사하였다. 당뇨병적인 증상이 관찰된 쥐를 30주부터 60주까지 혈당과 체중을 측정하였고, 희생 후 신장을 적출하여 형태학적인 변화를 관찰하고, TGF-β1에 대한 면역조직화적 염색 및 RT-PCR을 실시하여 TGF-β1의 발현 양과 발현 부위를 조사하였다. 결과 : 37주째의 혈당은 OLETF 쥐와 LETO 쥐에서 각각 237 mg/dL와 131 mg/dL이었으며, 체중에 있어서는 OLETF쥐가 LETO에 비하여 유의하게 증가하였다. HE염색을 통한 형태학적 관찰에서는 60주까지도 사구체경화는 확인되지 않았다. 그러나 TGF-β1에 대한 면역조직화학적 염색 결과, 30주에서 40주까지의 OLETF 쥐에서 사구체 내피세포에서 TGF-β1이 발현됨을 확인할 수 있었고, 37주부터는 세뇨관 상피세포에서도 TGF-β1의 발현을 확인할 수 있었다. 60주 OLETF 쥐의 사구체 내피세포에서는 TGF-β1의 발현은 없었으나, 세뇨관 상피세포에서는 많은 양의 TGF-β1의 발현을 관찰할 수 있었다. 30주째의 OLETF 쥐와 LETO 쥐로부터 RNA를 분리하여 TGF-β1 mRNA에 대한 RT-PCR 결과, LETO 쥐에 비하여 OLETF 쥐에서 TGF-β1 mRNA의 발현이 의의있게 많았다. 대조군인 LETO 쥐는 유의할 만한 TGF-β1의 발현이 없었다. 결론 : 본 연구에서 OLETF 쥐의 사구체 섬유화는 60주까지도 매우 느리게 진행되었으나, 30주 이후에 혈당과 TGF-β1의 발현은 크게 증가하였다. OLETF 쥐 37주째부터는 TGF-β1의 발현이 사구체 내피세포에서 뿐만 아니라 세뇨관 상피세포에서도 과다 발현되는 것을 확인할 수 있었다. Background : Diabetic nephropathy is a common cause of end-stage renal disease by means of glomerular and interstitial fibrosis. Increases in extracellular matrix (ECM) and changes in its components have been documented in the glomeruli of diabetic nephropath. Fibrogenic cytokines, particularly transforming growth factor (TGF)-β1, play a central role in progressive renal fibrosis. Activated TGF-β1 is known to increase the production of ECM as collagen and fibronectin. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an inbred strain that spontaneously develops non-insulin-depentent diabets mellitus which progresses to diabetic glomerulosclerosis. This study is examined the time points and localization of TGF-β1 in diabetic glomerulosclerosis of OLETF rats. Methods : OLETF rats, a chronic model for human type 2 diabetes mellitus, and age-matched control (LETO) rats were used. Blood was assayed for glouse and body weight were measured. From rats aged 30 to 60 weeks, animals were sacrificed under ether anesthesia, and both kidneys were removed. Portions of these tissues were processed for light microscopy and immunohistochemistry of TGF-β1. TGF-β1 mRNA levels were measured by reverse transcription polymerase chain reaction. Results : The body weights of OLETF rats were significantly greater than those of LETO rats from the age of 30 to 40 weeks, but those of OLETF rats gradually decreased after 40 weeks of age. There were no differences in body weights between these two strains at 50 weeks of age. Blood glucose levels of OLETF rats increased significantly with aging and were significantly higher than those of LETO rats after 32 weeks of age. There was no significant fibrosis in kidney of OLETF and LETO rats at all ages examined. The TGF-β1 protein was detected in the glomerular endothelial cells and tubular epithelial cells of OLETF rats at 35 to 38 weeks of age. The TGF-β1 protein in tubular epithelial cells of OLETF rats was strongly expressed at 60 weeks of age, whereas the glomerular endothelial cells scarcely detected the expression of TGF-β1 protein. In LETO rat kidneys, the TGF-β1 protein is detected in the glomerular endothelial cells at 35 weeks of ages, but is not detected in any other cells. The TGF-β1 mRNA of OLETF rats were increased at 32 weeks of age, higher than that of control LETO rats. Conclusion : Until 60 weeks of age, glomerular sclerosis became very weakly in OLETF rats. However, in 30-week-old OLETF rats, the blood gloucose levels and TGF-β1 protein increased significantly. The TGF-β1 protein was detected in the glomerular endothelial cells and tubular epithelial cells of OLETF rats at 37 weeks of age.