scholarly journals Transforming growth factor-β1 and activin A generate antiproliferative signaling in thyroid cancer cells

2006 ◽  
Vol 190 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Sílvia Emiko Matsuo ◽  
Suzana Garcia Leoni ◽  
Alison Colquhoun ◽  
Edna Teruko Kimura
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Carcinoma Cell ◽  
Transforming Growth Factor Β1 ◽  
Activin A ◽  
Antiproliferative Signaling ◽  
Tgf Β1

Transforming growth factor-beta 1 (TGF-β1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-β1 is a potent antimitogenic factor for thyroid follicular cells, while the role of ActA is not clear. In our study, the proliferation of TPC-1, the papillary thyroid carcinoma cell line, was reduced by both recombinant ActA and TGF-β1. Due to the concomitant expression of TGF-β1 and ActA in thyroid tumors, we investigated the effects of either TGF-β1 or ActA gene silencing by RNA interference in TPC-1 cells in order to distinguish the specific participation of each in proliferation and intracellular signaling. An increased proliferation and reduced SMAD2, SMAD3, and SMAD4 mRNA expression were observed in both TGF-β1 and ActA knockdown cells. Recombinant TGF-β1 and ActA increased the expression of inhibitory SMAD7, whereas they reduced c-MYC. Accordingly, we detected a reduction in SMAD7 expression in knockdown cells while, unexpectedly, c-MYC was reduced. Our data indicate that both TGF-β1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-β1 and ActA have an antiproliferative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.

Growth factor expression pattern of homologous feeder layer for culturing buffalo embryonic stem cell-like cells

2012 ◽  
Vol 24 (8) ◽  
pp. 1098 ◽  
Author(s):  
Ruchi Sharma ◽  
Aman George ◽  
Nitin M. Kamble ◽  
Manmohan S. Chauhan ◽  
Suresh Singla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Embryonic Stem ◽  
Transforming Growth Factor Β1 ◽  
Activin A ◽  
Feeder Layer ◽  
Es Cell ◽  
Fetal Fibroblasts ◽  
Tgf Β1

The present study examined the expression profile of buffalo fetal fibroblasts (BFF) used as a feeder layer for embryonic stem (ES) cell-like cells. The expression of important growth factors was detected in cells at different passages. Mitomycin-C inactivation increased relative expression levels of ACTIVIN-A, TGF-β1, BMP-4 and GREMLIN but not of fibroblast growth factor-2 (FGF-2). The expression level of ACTIVIN-A, transforming growth factor-β1 (TGF-β1), bone morphogenetic protein-4 (BMP-4) and FGF-2 was similar in buffalo fetal fibroblast (BFF) cultured in stem cell medium (SCM), SCM + 1000 IU mL–1 leukemia inhibitory factor (LIF), SCM + 5 ng mL–1 FGF-2 or SCM + LIF + FGF-2 for 24 h whereas GREMLIN expression was higher in FGF-2-supplemented groups. In spent medium, the concentration of ACTIVIN-A was higher in FGF-2-supplemented groups whereas that of TGF-β1 was similar in SCM and LIF + FGF-2, which was higher than when either LIF or FGF-2 was used alone. Following culture of ES cell-like cells on a feeder layer for 24 h, the TGF-β1 concentration was higher with LIF+FGF-2 than with LIF or FGF-2 alone which, in turn, was higher than that in SCM. In the LIF + FGF-2 group, the concentration of TGF-β1 was lower and that of ACTIVIN-A was higher in spent medium at 24 h than at 48 h of culture. These results suggest that BFF produce signalling molecules that may help in self-renewal of buffalo ES cell-like cells.

scholarly journals Hepatitis B virus X antigen promotes transforming growth factor-β1 (TGF-β1) activity by up-regulation of TGF-β1 and down-regulation of α 2-macroglobulin

2004 ◽  
Vol 85 (2) ◽  
pp. 275-282 ◽  
Author(s):  
Jingbo Pan ◽  
Marcy Clayton ◽  
Mark A. Feitelson
Keyword(s):  
Hepatitis B Virus ◽  
Growth Factor ◽  
Hepatitis B ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Sensitive Cell Line ◽  
Cdna Subtraction ◽  
B Virus ◽  
Tgf Β1

Hepatitis B virus (HBV) X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by activation of signalling pathways such as NF-κB. To identify NF-κB target genes differentially expressed in HBxAg-positive compared to -negative cells, HepG2 cells consistently expressing HBxAg (HepG2X cells) were stably transfected with pZeoSV2 or pZeoSV2-IκBα. mRNA from each culture was isolated and compared by PCR select cDNA subtraction. The results showed lower levels of α 2-macroglobulin (α 2-M) in HepG2X-pZeoSV2 compared to HepG2X-pZeoSV2-IκBα cells. This was confirmed by Northern and Western blotting, and by measurement of extracellular α 2-M levels. Elevated transforming growth factor-β1 (TGF-β1) levels were also seen in HepG2X compared to control cells. Serum-free conditioned medium (SFCM) from HepG2X cells suppressed DNA synthesis in a TGF-β-sensitive cell line, Mv1Lu. The latter was reversed when the SFCM was pretreated with exogenous, activated α 2-M or with anti-TGF-β. Since elevated TGF-β1 promotes the development of many tumour types, these observations suggest that the HBxAg-mediated alteration in TGF-β1 and α 2-M production may contribute importantly to the pathogenesis of HCC.

scholarly journals HUBUNGAN ANTARA KADAR TGF-Β1 DENGAN KADAR ALBUMIN DALAM URIN PASIEN DM TIPE-2 DENGAN NEFROPATI DIABETIK

2019 ◽  
Vol 7 (1) ◽  
pp. 73-81
Author(s):  
Elfiani Elfiani ◽  
Rita Halim ◽  
M Haldian Hakir
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Albumin Level ◽  
Cross Sectional ◽  
Integrin Linked Kinase ◽  
Tgf Β1

ABSTRACT Background: Diabetic nephropathy (DN) is a complication of diabetes in the kidney that frequently causes terminal kidney disease. This kidney disease caused by diabetes is a syndrome characterized by albumin in urine (albuminuria). Growth factor-β1 (TGF- β1) is a multifunctional cytokine that controls many biological processes, including immunity, differentiation, tumor suppression, tumor metastasis, aging, migration, wound healing, apoptosis, adipogenesis, and osteogenesis. Previous studies had showed that TGF-β1 plays a role in albuminuria, where TGF-β1 expression in the kidney increases in diabetes patients. Elevation of cytokine level, especially transforming growth factor beta-1 (TGF-β1) that induces the increase of several extra cellular matrices (ECM), i.e. fibronectin, integrin-linked kinase (ILK) and type IV collagen. This TGF-β1 activity causes the accumulation of ECM, which leads to thickened glomerular basement membrane (GBM). Thickening of GBM and changes in kidney structure in the form of hypertrophy and reduced glomerular podocytes caused by apoptosis and attachment in GBM causes protein components to exit through urine (albuminuria). This study aimed to prove the correlation between transforming growth factor-β1 and albumin level in urine of diabetic nephropathy. Metode : This study a observasional with desain Cross-sectional  comparative study. Results: Mean TGF-β1 level in type 2 DM patients with diabetic nephropathy in this study was 47.30 ± 14.70 ng/ml, with similar value between men and women with 43.1 ng/ml and 44.7 ng/ml, respectively. Out of 60 type 2 DM participants with ND, the mean albuminuria level according to ACR was 722.53 ± 1854.96 mg/g. The result of male participants was lower compared to female participants, with 667.8 mg/mg and 777.2 mg/g, respectively. Conclusion: There was insignificant correlation between TGF-β1 in diabetic nephropathy (DN) and albumin level in urine measured using albumin and urine creatinine ratio (ACR) (p = 0.066). Keywords: Diabetic Nephropathy, Albuminuria, TGF-β1   ABSTRAK Latar Belakang : Nefropati diabetik (ND) merupakan komplikasi diabetes pada ginjal yang paling sering menyebabkan terjadinya penyakit ginjal terminal. Penyakit ginjal akibat diabetes ini merupakan sindroma dengan karakteristik terdapatnya albumin dalam urine (albuminuria). Faktor pertumbuhan-β1 (TGF-β1) adalah sebuah sitokin multifungsi yang mengendalikan banyak proses biologis termasuk kekebalan, diferensiasi, tumor supresi, tumor metastasis, penuaan, migrasi, penyembuhan luka, apoptosis, adipogenesis, dan osteogenesis. Sejumlah penelitian sebelumnya menunjukkan bahwa TGF-β1 berperan terhadap terjadinya albuminuria, dimana pasien diabetes didapatkan ekspresi TGF-β1 di ginjal meningkat. Peningkatan kadar cytokine terutama Transforming Growth Factor Beta-1 (TGF-β1) yang menginduksi peningkatan beberapa Extra Cellular Matrix (ECM) antara lain fibronectin, integrin-linked kinase (ILK) dan collagen tipe-IV. Aktifitas TGF-β1 ini menyebabkan akumulasi ECM sehingga terjadi penebalan Glomerular Basement Membrane (GBM). Penebalan dari GBM dan terjadinya perubahan struktur ginjal berupa hipertrofi dan berkurangnya sel-sel podocyte glomerulus akibat kerusakan (apoptosis) dan perlengketan di GBM menyebabkan komponen protein keluar melalui urin (albuminuria). Tujuan penelitian ini untuk membuktikan hubungan antara kadar transforming growth  factor-β1 dengan kadar albumin dalam urin pada Nefropati Diabetik. Metode : Penelitian ini merupakan penelitian Observasional dengan desain Cross-sectional   comparative study. Hasil : Kadar rata-rata TGF-β1 pasien DM tipe-2 dengan Nefropati Diabetik pada penelitian ini adalah 47,30 ± 14,70 ng/ml, tidak jauh berbeda antara laki-laki yaitu 43,1 ng/ml dengan perempuan 44,7 ng/ml. Dari 60 orang responden DM tipe-2 dengan ND pada penelitian ini didapatkan kadar albuminuria rata-rata berdasarkan ACR adalah 722,53 ± 1854,96 mg/g. Responden laki-laki lebih rendah dibanding perempuan yaitu 667,8 mg/g berbanding 777,2 mg/g. Kesimpulan : Tidak terdapat hubungan yang bermakna antara TGF-β1 pada Nefropati Diabetik (ND) dengan kadar albumin dalam urin yang dihitung berdasarkan rasio albumin dan creatinin urin (ACR) (p=0,066). Kata Kunci : Nefropati Diabetik, Albuminuria, TGF-β1

Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kanagaraj Gomathi ◽  
Muthukumar Rohini ◽  
Nicola C. Partridge ◽  
Nagarajan Selvamurugan
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Bone Development ◽  
Osteoblastic Cells ◽  
Post Translational Modification ◽  
Matrix Metalloproteinase 13 ◽  
Tgf Β1

Abstract Transforming growth factor beta 1 (TGF-β1) functions as a coupling factor between bone development and resorption. Matrix metalloproteinase 13 (MMP13) is important in bone remodeling, and skeletal dysplasia is caused by a deficiency in MMP13 expre-ssion. Runx2, a transcription factor is essential for bone development, and MMP13 is one of its target genes. TGF-β1 promoted Runx2 phosphorylation, which was necessary for MMP13 production in osteoblastic cells, as we previously shown. Since the phosphorylation of some proteins causes them to be degraded by the ubiquitin/proteasome pathway, we hypothesized that TGF-β1 might stabilize the phosphorylated Runx2 protein for its activity by other post-translational modification (PTM). This study demonstrated that TGF-β1-stimulated Runx2 acetylation in rat osteoblastic cells. p300, a histone acetyltransferase interacted with Runx2, and it promoted Runx2 acetylation upon TGF-β1-treatment in these cells. Knockdown of p300 decreased the TGF-β1-stimulated Runx2 acetylation and MMP13 expression in rat osteoblastic cells. TGF-β1-treatment stimulated the acetylated Runx2 bound at the MMP13 promoter, and knockdown of p300 reduced this effect in these cells. Overall, our studies identified the transcriptional regulation of MMP13 by TGF-β1 via Runx2 acetylation in rat osteoblastic cells, and these findings contribute to the knowledge of events presiding bone metabolism.

Transforming growth factor-β1 downregulation of Smad1 gene expression in rat hepatic stellate cells

2003 ◽  
Vol 285 (3) ◽  
pp. G539-G546 ◽  
Author(s):  
Hong Shen ◽  
Guojiang Huang ◽  
Mohammed Hadi ◽  
Patrick Choy ◽  
Manna Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Dependent Manner ◽  
Tgf Β1

Smads are intracellular signaling molecules of the transforming growth factor-β (TGF-β) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-β significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-β1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-β1 significantly inhibits the expression of the Smad1 gene.

scholarly journals Transforming Growth Factor β1 and Tropoelastin Expression in Uterine Prolapse

2016 ◽  
pp. 70
Author(s):  
Alvilusia Alvilusia ◽  
Amir Fauzi ◽  
Azhari Azhari ◽  
Wresnindyatsih Wresnindyatsih ◽  
Irsan Saleh
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Uterine Prolapse ◽  
Transforming Growth Factor Β1 ◽  
Moderate Correlation ◽  
Cross Sectional ◽  
Positive Correlation ◽  
Growth Factor Beta ◽  
Tgf Β1

Objective: To know the correlation of the expression of transforming growth factor beta (TGF-β1) and tropoelastin in uterine prolapse. Method: A cross-sectional study of 30 subjects suffered from uterine prolapse in the Department of Obstetrics and Gynecology Dr. Mohammad Hoesin hospital Palembang. The study was conducted since December 1st, 2014 until July 31st, 2015. The sample was from the sacrouterine ligament and immunohistochemical examination was conducted to see the expression of TGF-β1 and tropoelastin. Result: Of the 30 subjects obtained, the expression of TGF-β1 was on 30 subjects consisting of 18 (60%) for weak expression and 12 (40%) for strong expression. Meanwhile, the strong tropoelastin expression was on 18 subjects (60%) and weak tropoelastin expression on 12 subjects (40%). There was a positive correlation between TGF-β1 and tropoelastin expression with moderate correlation (p=0.014; r=0.44). Conclusion: There is a positive correlation between the TGF-β1 and tropoelastin expression of sacrouterine ligament in uterine prolapse with moderate correlation. [Indones J Obstet Gynecol 2016; 4-2: 70-74] Keywords: transforming Growth Factor Beta 1, tropoelastin, uterine prolapse

scholarly journals Transforming growth factor-β1 selectively inhibits hepatocyte growth factor expression via a micro-RNA-199–dependent posttranscriptional mechanism

2013 ◽  
Vol 24 (13) ◽  
pp. 2088-2097 ◽  
Author(s):  
Ognoon Mungunsukh ◽  
Regina M. Day
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Micro Rna ◽  
Luciferase Reporter ◽  
And Migration ◽  
Hepatocyte Growth ◽  
Tgf Β1

Hepatocyte growth factor (HGF) is a multipotent endogenous repair factor secreted primarily by mesenchymal cells with effects on cells expressing its receptor, Met. HGF promotes normal tissue regeneration and inhibits fibrotic remodeling in part by promoting proliferation and migration of endothelial and epithelial cells and protecting these cells from apoptosis. HGF also inhibits myofibroblast proliferation. The profibrotic cytokine transforming growth factor beta 1 (TGF-β1) suppresses HGF expression but not the expression of NK2, an HGF splice variant that antagonizes HGF-induced proliferation. We investigated the mechanism for differential regulation of HGF and NK2 by TGF-β1. TGF-β1 down-regulated HGF in primary human adult pulmonary fibroblasts (HLFb) and increased the expression of miR-199a-3p, a microRNA (miRNA) associated with fibrotic remodeling. HGF and NK2 contain completely different 3′ untranslated regions (UTRs), and we determined that miR-199a-3p targeted HGF mRNA for suppression but not NK2. A pre–miR-199 mimic inhibited the expression of a luciferase reporter harboring the HGF 3′ UTR but not a pmirGLO reporter containing the NK2 3′ UTR. In contrast, an anti-miRNA inhibitor specific for miR-199a-3p prevented TGF-β1–induced reduction of both HGF mRNA and HGF protein secretion. Taken together, these findings demonstrate that HGF is distinctly regulated at the posttranscriptional level from its antagonist NK2.

scholarly journals Penggunaan Tetes Telinga Serum Autologous dengan Amnion untuk Penutupan Perforasi Membran Timpani

2012 ◽  
Vol 1 (1) ◽  
Author(s):  
Hidayatul Fitria ◽  
Yan Edward
Keyword(s):  
Growth Factor ◽  
Tympanic Membrane ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Tympanic Membrane Perforation ◽  
Autologous Serum ◽  
Membrane Perforation ◽  
Epidermal Growth ◽  
Tgf Β1

Abstrak Latar Belakang: Gangguan pendengaran atau ketulian mempunyai dampak yang merugikan bagi penderita , keluarga, masyarakat maupun negara. Salah satu penyebab ketulian yang sering dijumpai adalah radang telinga tengah, terutama yang disertai perforasi membran timpani yang menetap. Penutupan perforasi membran timpani dapat dilakukan dengan operatif dan konservatif. Secara konservatif sudah banyak cara yang dilakukan. Salah satunya dengan mengkaustik tepi perforasi dengan menggunakan silver nitrat untuk membuat luka baru, kemudian digunakan amnion sebagai jembatan (bridge) dan faktor regulasi yang terdapat pada tetes telinga serum autologous. Tujuan: Untuk menjelaskan gambaran penggunaan amnion sebagai jembatan dan tetes telinga serum autologous sebagai faktor regulasi. Tinjauan pustaka: Penutupan perforasi membran timpani dapat dilakukan secara konservatif salah satunya dengan menggunakan tetes telinga serum autologous sebagai faktor regulator, amnion sebagai jembatan dan penggunaan silver nitrat pada tepi perforasi untuk membuat luka baru. Serum autologous memiliki asselerator pertumbuhan yaitu epidermal growth factor (EGF) , transforming growth factor β1 (TGF- β1) dan fibronektin. Asselerator pertumbuhan ini dapat kita temukan pada penyembuhan membran timpani normal. Sedangkan membran amnion adalah jaringan semi transparan tipis yang membentuk lapisan terdalam membran fetus dengan susunan membran basalis yang tebal dan jaringan stroma avaskuler. Membran amnion mempercepat pembentukan epitel normal dengan menekan pembentukan jaringan fibrosis. Sel epitel amnion memproduksi faktor pertumbuhan seperti fibroblast growth factor dan transforming growth factor beta. Faktor pertumbuhan akan membantu komunikasi antara epitel dan sel fibroblast stroma untuk menekan proliferasi dan diferensiasi jaringan fibrosis. Kesimpulan: Diperlukan tiga elemen pada penutupan perforasi membran timpani yaitu faktor regulasi, jembatan (bridge) dan membuat luka baru pada tepi perforasi. Kata kunci: tetes telinga serum autologous, membran amnion, perforasi membran timpani Abstract Background: Hearing loss or deafness have an adverse impact on patients, families, communities and the country. One cause of deafness that often met is middle ear inflammation, especially those with persistent tympanic membrane perforation. Closure of tympanic membrane perforation can be performed with operative and conservative. The conservatives have done with a lot of ways. One of them is cauterize edge of perforation by using silver nitrate to make a new wound, then used the amnion as a bridge and regulatory factors present in autologous serum eardrops. Objective: To describe the use of amnion as a bridge and autologous serum eardrops as a regulatory factor. Literature review: Closure of tympanic membrane perforation conservatively can be done either by using the autologous serum eardrops as a factor regulator, amnion as a bridge and the use of silver nitrate on the edge of the perforation to create a new wound. Autologous serum have asselator growth of Epidermal Growth Factor (EGF), Transforming Growth Factor β1 (TGF-β1) and fibronectin. Asselerator growth factor can be found on normal tympanic membrane healing. While the amniotic membrane is semi-transparant thin tissue that forms the deepest layer of fetal membranes with formation of a thick basement membrane and tissue stroma avaskuler. Amniotic membrane accelerate the formation of normal epithelial tissue by pressing the formation of fibrosis. Amniotic epithelial cells produce growth factors such as fibroblast growth factor and transforming growth factor beta. Growth factors will help the communication between epithelial and stromal fibroblast cells to suppress proliferation and differentiation of tissue fibrosis. Conclusion: It takes three elements on the closure of tympanic membrane perforation factor regulation, bridge and make new cuts on the edge of the perforation. Keywords: autologous serum eardrops, amnion membrane, tympanic membrane perforation

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