scholarly journals Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

1997 ◽  
Vol 322 (3) ◽  
pp. 809-814 ◽  
Author(s):  
Kazushi IMAI ◽  
Ari HIRAMATSU ◽  
Daikichi FUKUSHIMA ◽  
Michael D. PIERSCHBACHER ◽  
Yasunori OKADA
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Transforming Growth Factor ◽  
Core Protein ◽  
Chondroitin Sulphate ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Extracellular Milieu ◽  
Tissue Reactions ◽  
Tgf Β1

Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a role in regulation of collagen fibrillogenesis and function as a reservoir of transforming growth factor β(TGF-β) in the extracellular milieu. We have examined the susceptibility of DCN to five different matrix metalloproteinases (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern. The N-terminal sequence of the two fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The values of Km for the MMPs capable of degrading DCN are very similar (10–12 μM), but the kcat/Km value for MMP-7 (30.5 μM-1·h-1) is 4.5-fold higher than those for MMP-2 and MMP-3. Incubation of a DCN–TGF-β1 complex with MMP-2, -3 or -7 results in release of TGF-β1 from the complex. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-β1 released from DCN in the connective tissues.

scholarly journals Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily

2012 ◽  
Vol 3 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Nanako Kawaguchi
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
Methyl Cellulose ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Cardiac Stem Cells ◽  
Dependent Manner ◽  
Tgf Β1

AbstractHeart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.

scholarly journals TGF-β1 869T/C Polymorphism and Ischemic Stroke: Sex Difference in Chinese

2010 ◽  
Vol 37 (6) ◽  
pp. 803-807 ◽  
Author(s):  
Hong-miao Tao ◽  
Guo-zhong Chen ◽  
Xiao-dong Lu ◽  
Gan-ping Chen ◽  
Bei Shao
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Chinese Patients ◽  
Cerebrovascular Complications ◽  
Specific Association ◽  
Female Specific ◽  
Tgf Β1

AbstractBackground:Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cerebrovascular complications. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine with a central role in inflammation. To investigate whether polymorphisms of the TGF-β1 gene can modify the risk of ischemic stroke (IS) in Chinese population, we conduct this hospital-based, case-control study.Methods:Transforming growth factor-β1 genotype was determined in 450 Chinese patients (306 male and 144 female) with IS and 450 control subjects (326 male and 124 female).Results:Subjects carrying 869TT were susceptible to IS (odds ratio [OR] =1.58; P=0.003). Further analysis of IS data partitioned by gender revealed the female-specific association with 869T/C (OR=2.64; P=0.001).Conclusions:Findings suggest that the TT genotype of 869T/C might be a risk factor of IS in Chinese, especially in females.

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 Non-uniform influence of transforming growth factor-β on the biosynthesis of different forms of small chondroitin sulphate/dermatan sulphate proteoglycan

1990 ◽  
Vol 269 (2) ◽  
pp. 551-554 ◽  
Author(s):  
B Breuer ◽  
G Schmidt ◽  
H Kresse
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Core Protein ◽  
Chondroitin Sulphate ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Osteosarcoma Cell ◽  
Tgf Beta ◽  
Small Proteoglycan

The influence of transforming growth factor-beta (TGF-beta) on the expression of different forms of small proteoglycans was investigated in human skin fibroblasts and in a human osteosarcoma cell line. TGF-beta was not found to act as a general stimulator of small proteoglycan biosynthesis. In both cell types, an increased expression of the core protein of proteoglycan I was found. However, there was a profound decrease in the expression of a 106 kDa core protein, and either no alteration or a small decrease in the biosynthesis of the collagen-binding small proteoglycan II core protein. These results show that the production of individual members of the small proteoglycan family is differentially regulated.

scholarly journals Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor β Signaling Pathway by Binding to SMAD3

2006 ◽  
Vol 80 (24) ◽  
pp. 12420-12424 ◽  
Author(s):  
Jose-Andres Mendoza ◽  
Yves Jacob ◽  
Patricia Cassonnet ◽  
Michel Favre
Keyword(s):  
Human Papillomavirus ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cellular Transformation ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
E6 Oncoprotein ◽  
E6 Protein ◽  
Tgf Β1

ABSTRACT Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor β1 (TGF-β1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-β1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.

scholarly journals BLOOD MATRIX METALLOPROTEINASES LEVELS IN CYSTIC FIBROSIS CHILDREN (TEN YEARS OBSERVATION)

2019 ◽  
Vol 21 (5) ◽  
pp. 279-284
Author(s):  
Maksim S. Egorov
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Blood Serum ◽  
Transforming Growth Factor ◽  
Reference Group ◽  
Transforming Growth Factor Β1 ◽  
Long Time ◽  
Ct Data ◽  
Tgf Β1

Introduction. Destructive fibrotic changes in lung tissue play a key role in the pathogenesis of cystic fibrosis (CF) in children. The development of pulmonary fibrosis may be caused by a violation of the pattern of matrix metalloproteinases (MMPs) and elevated production of profibrogenic growth factors (TGF-β1). Aim of the study. To compare the peculiarities of MMP patterns and transforming growth factor TGF-β1 with the data of the visualisation of airways features in cystic fibrosis (CF) children. Patients and Methods. The study included 80 inpatients aged of from 3 months to 18 years suffered from СF with the involvement of the lungs and digestive system observed for ten years. All patients were administered antibiotics (cefoperazone/sulbactam, ceftazidime, tienam, meropenem, amikacin) and inhalation (colisthmethate sodium, tobramycin) intravenously for a long time period. The reference group consisted of 16 children without pulmonary pathology. Blood serum concentrations of transforming growth factor-β1 (TGF-β1), matrix metalloproteinases (MMP-2, MMP-8, MMP-9) and tissue inhibitor of matrix metalloproteinases (TIMP-1) were determined by ELISA method. The morphological features of airways were evaluated by means of computer tomography (CT) with (GE Discovery CT750 HD). Results. In CF children patients blood serum MMP9 levels were significantly higher whereas TIMP-1 and MMP-2 appeared to be less than in children with intact airways. TGF-β1 levels in CF children were 9.8 times more than in cases from the reference group. CT data showed the pronounced changes in the airways structure as multiple bronchoectasias and pneumofibrosis. Conclusion. The revealed morphologic signs of the deterioration in airways’ structure in СF children patients can be related to the elevation of the rate of the fibrosis development due to the violation in the MMP and profibrogenic factors patterns and transforming growth factor TGF-β1.

scholarly journals Transforming Growth Factor β1 Induces Apoptosis through Cleavage of BAD in a Smad3-Dependent Mechanism in FaO Hepatoma Cells

2002 ◽  
Vol 22 (5) ◽  
pp. 1369-1378 ◽  
Author(s):  
Byung-Chul Kim ◽  
Mizuko Mamura ◽  
Kyeong Sook Choi ◽  
Bruno Calabretta ◽  
Seong-Jin Kim
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Hepatoma Cell ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Hepatoma Cell Line ◽  
Steady State Levels ◽  
Induced Apoptosis ◽  
Tgf Β1 ◽  
Dependent Mechanism

ABSTRACT Transforming growth factor β (TGF-β) induces apoptosis in a variety of cells. We have previously shown that TGF-β1 rapidly induces apoptosis in the FaO rat hepatoma cell line. We have now studied the effect of TGF-β1 on the expression of different members of the Bcl-2 family in these cells. We observed no detectable changes in the steady-state levels of Bcl-2, Bcl-XL, and Bax. However, TGF-β1 induced caspase-dependent cleavage of BAD at its N terminus to generate a 15-kDa truncated protein. Overexpression of the 15-kDa truncated BAD protein enhanced TGF-β1-induced apoptosis, whereas a mutant BAD resistant to caspase 3 cleavage blocked TGF-β1-induced apoptosis. Overexpression of Smad3 dramatically enhanced TGF-β1-induced cleavage of BAD and apoptosis, whereas antisense Smad3 blocked TGF-β1-induced apoptosis and BAD cleavage. These results suggest that TGF-β1 induces apoptosis through the cleavage of BAD in a Smad3-dependent mechanism.

scholarly journals PROTECTIVE EFFECT OF DIOSGENIN AGAINST CARBON TETRACHLORIDE AND CISPLATIN INDUCED HEPATOTOXICITY IN RATS

2018 ◽  
Vol 4 (3) ◽  
pp. 50-56
Author(s):  
Vikram V Nimbalkar ◽  
Ravina P Shelke ◽  
Urmila E Kadu ◽  
Pandurang M Gaikwad
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Liver Weight ◽  
Transforming Growth Factor Β1 ◽  
Serum Enzymes ◽  
Steroidal Saponin ◽  
Tgf Β1

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bilirubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4 and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation. 

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