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 MATRIX METALLOPROTEINASES IN CHILDREN WITH CYSTIC FIBROSIS

2019 ◽  
Vol 21 (3) ◽  
pp. 145-151
Author(s):  
I. E. Smirnov ◽  
A. G. Kucherenko ◽  
M. S. Egorov ◽  
G. I. Smirnova ◽  
Tsevegmid Urtnasan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Matrix Metalloproteinases ◽  
Blood Serum ◽  
Transforming Growth Factor ◽  
Reference Group ◽  
Transforming Growth Factor Β1 ◽  
Healthy Children ◽  
Elisa Method ◽  
Tgf Β1

The data of examination of 80 in-patients with the mixed form of cystic fibrosis (CF) are presented. All cases were divided into 3 groups according to the severity of the course of the disease. 16 conditionally healthy children made up a reference group. Determination of blood serum concentrations of interleukins (IL4, IL6), transforming growth factor-β1 (TGF-β1), matrix metalloproteinases MMP-2, MMP-8, MMP-9 and tissue inhibitor-TIMP-1 was performed by immunoassay ELISA method. The changes in the content of MMP and TIMP-1 in the blood serum of patients with various severity of the course of CF were found to be characterized by a significant decrease in MMP-8 and TIMP-1 concentrations, an increase in MMP-2 levels in children with moderate СF and a significant increase in MMP-9 concentrations, especially pronounced in patients with severe CF. At the same time, no definite dependence of the changes in MMP and TIMP-1 concentrations in the blood serum of patients on the frequency of exacerbations in the CF course and the dominant microbiota was found. Changes in the content of IL and TGF-β1 in the blood serum of children with the various severity of the course of CF were characterized by an increase in the concentrations of IL4 and TGFβ1 by more than 9.8 times, and IL6 - by 4.6 times if compared with the reference group. However, there no direct correlation was found between the changes in their production and the severity of the course of CF. The authors believe elevated levels of MMP, TIMP, and altered relationships between them can be used as biomarkers of the exacerbation of CF course in children.

scholarly journals Transforming growth factor-β1 impairs CFTR-mediated anion secretion across cultured porcine vas deferens epithelial monolayer via the p38 MAPK pathway

2013 ◽  
Vol 305 (8) ◽  
pp. C867-C876 ◽  
Author(s):  
Sheng Yi ◽  
Fernando Pierucci-Alves ◽  
Bruce D. Schultz
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Vas Deferens ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Anion Secretion ◽  
Tgf Β1

The goal of this study was to determine whether transforming growth factor-β1 (TGF-β1) affects epithelial cells lining the vas deferens, an organ that is universally affected in cystic fibrosis male patients. In PVD9902 cells, which are derived from porcine vas deferens epithelium, TGF-β1 exposure significantly reduced short-circuit current ( Isc) stimulated by forskolin or a cell membrane-permeant cAMP analog, 8-pCPT-cAMP, suggesting that TGF-β1 affects targets of the cAMP signaling pathway. Electrophysiological results indicated that TGF-β1 reduces the magnitude of current inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) channel blockers. Real-time RT-PCR revealed that TGF-β1 downregulates the abundance of mRNA coding for CFTR, while biotinylation and Western blot showed that TGF-β1 reduces both total CFTR and apical cell surface CFTR abundance. These results suggest that TGF-β1 causes a reduction in CFTR expression, which limits CFTR-mediated anion secretion. TGF-β1-associated attenuation of anion secretion was abrogated by SB431542, a TGF-β1 receptor I inhibitor. Signaling pathway studies showed that the effect of TGF-β1 on Isc was reduced by SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). TGF-β1 exposure also increased the amount of phospho-p38 MAPK substantially. In addition, anisomycin, a p38 MAPK activator, mimicked the effect of TGF-β1, which further suggests that TGF-β1 affects PVD9902 cells through a p38 MAPK pathway. These observations suggest that TGF-β1, via TGF-β1 receptor I and p38 MAPK signaling, reduces CFTR expression to impair CFTR-mediated anion secretion, which would likely compound the effects associated with mild CFTR mutations and ultimately would compromise male fertility.

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 JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

2021 ◽  
Vol 22 (6) ◽  
pp. 2952
Author(s):  
Tzu-Yu Hou ◽  
Shi-Bei Wu ◽  
Hui-Chuan Kau ◽  
Chieh-Chih Tsai
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Mitogen Activated Protein Kinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Western Blots ◽  
Orbital Fibroblasts ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.

scholarly journals Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yueyi Yang ◽  
Wenjing Liu ◽  
JieYa Wei ◽  
Yujia Cui ◽  
Demao Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gap Junction ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cx43 Expression ◽  
Mc3t3 Cell ◽  
Primary Osteoblasts ◽  
Tgf Β1 ◽  
Cell Cell

AbstractGap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-α Signaling

2001 ◽  
Vol 21 (21) ◽  
pp. 7218-7230 ◽  
Author(s):  
Francesc Viñals ◽  
Jacques Pouysségur
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Cell Survival ◽  
Network Formation ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
In Vitro Angiogenesis ◽  
Tgf Β1

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Suppresses Growth of B-cell Lymphoma Cells by p14ARF-dependent Regulation of Mutant p53

2012 ◽  
Vol 287 (27) ◽  
pp. 23184-23195 ◽  
Author(s):  
Gang Chen ◽  
Paritosh Ghosh ◽  
Thomas O'Farrell ◽  
Rachel Munk ◽  
Louis J. Rezanka ◽  
...  
Keyword(s):  
Growth Factor ◽  
B Cell ◽  
Transforming Growth Factor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Transforming Growth Factor Β1 ◽  
Mutant P53 ◽  
Lymphoma Cells ◽  
Tgf Β1
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