scholarly journals TGF-β1 and its signal molecules: are they correlated with the elasticity characteristics of breast lesions?

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng Ke Zhang ◽  
Bo Wang ◽  
Shi Yu Li ◽  
Gang Liu ◽  
Zhi Li Wang
Keyword(s):  
Protein Kinase ◽  
Diagnostic Performance ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Expression Level ◽  
Signal Molecules ◽  
Breast Lesions ◽  
Expression Levels ◽  
Elasticity Characteristics ◽  
Tgf Β1

Abstract Background Shear wave elastography can evaluate tissue stiffness. Previous studies showed that the elasticity characteristics of breast lesions were related to the components of extracellular matrix which was regulated by transforming growth factor beta 1(TGF-β1) directly or indirectly. However, the correlation of the expression level of TGF-β1, its signal molecules and elasticity characteristics of breast lesions have rarely been reported. The purpose of this study was to investigate the correlation between the expression level of TGF-β1, its signal molecules, and the elasticity characteristics of breast lesions. Methods 135 breast lesions in 130 patients were included. Elasticity parameters, including elasticity modulus, the elasticity ratio, the “stiff rim sign”, were recorded before biopsy and surgical excision. The expression levels of TGF-β1 and its signal molecules, including Smad2/3, Erk1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase 2 (JNK2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/AKT) were detected by immunohistochemistry. The diagnostic performance of the expression level of those molecules and their correlation with the elasticity characteristics were analyzed. Results Elasticity parameters and the expression levels of TGF- β1 and its signal molecules of benign lesions were lower than those of malignant lesions (P<0.0001). The expression levels of TGF- β1 and its signal molecules were correlated with elasticity parameters. The expression levels of TGF- β1 and its signal molecules in lesions with “stiff rim sign” were higher than those without “stiff rim sign” (P<0.05). And the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were correlated with that of TGF- β1. The area under the curve for receiver operator characteristic curve of TGF-β1 and its signal molecules in the differentiation of malignant and benign breast lesions ranged from 0.920–0.960. Conclusions The expression levels of TGF-β1, its signal molecules of breast lesions showed good diagnostic performance and were correlated with the elasticity parameters. The expression levels of signal molecules were correlated with that of TGF- β1, which speculated that TGF- β1 might play an important role in the regulation of breast lesion elasticity parameters and multiple signal molecule expressions.

scholarly journals The Antioxidant tempol delays the MIA-induced osteoarthritis progression in rats via modulation of signaling pathways involving TGF-β1/SMAD3/NOX4 axis

2021 ◽  
Author(s):  
Hagar B. Abo-zalam ◽  
Rehab F. Abdel-Rahman ◽  
Mohamed F. Abd-Ellah ◽  
Rania M. Abdalsalam ◽  
Mahmoud M. Khattab
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Matrix Protein ◽  
Structural Changes ◽  
Complex Disease ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Knee Oa ◽  
Nadph Oxidase 4 ◽  
Tgf Β1

Abstract Osteoarthritis (OA) is a complex disease characterized by structural, functional, and metabolic deteriorations of the whole joint and periarticular tissues. In the current study, we aimed to investigate the possible effects of tempol on knee OA induced by the chemical chondrotoxic monosodium iodoacetate (MIA) which closely mimics both the pain and structural changes associated with human OA. Rats were administrated oral tempol (100 mg/kg) one week post-MIA injection (3 mg/ 50 μL saline) at the right knee joints for 21 consecutive days. Tempol improved motor performance and debilitated the MIA-related radiological and histological alterations. Besides, it subsided the knee joint swelling. Tempol decreased the cartilage degradation-related biomarkers as matrix metalloproteinase-13, cartilage oligomeric matrix protein, and fibulin-3. The superoxide dismutase mimetic effect of tempol was accompanied by decreased NADPH oxidase 4 (NOX4), inflammatory mediators, nuclear factor kappa-B (NF-κB), over-released insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Tempol decreased the expression of chemotactic cytokine ligand 2 (CCL2), dickkopf‑related protein-1 (DKK-1), and protein kinase C (PKC). On the molecular level, tempol reduced the phosphorylated protein levels of p38 mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and small mother against decapentaplegic 3 homologs (SMAD3). These findings suggest the promising role of tempol in ameliorating MIA-induced knee OA in rats via collateral suppression of the catabolic signaling cascades including TGF-β1/SMAD3/NOX4, NOX4/p38MAPK/NF-κB, and PI3K/Akt/NF-κB and therefore modulation of oxidative stress, catabolic inflammatory cascades, chondrocyte metabolic homeostasis, autophagy, and cell survival.

scholarly journals TGF-β1 and Its Signal Transduction Pathways: Are They Corelated With The Elastic Characteristics of Breast Lesions?

2021 ◽  
Author(s):  
Meng Ke Zhang ◽  
Shi Yu Li ◽  
Bo Wang ◽  
Gang Liu ◽  
Zhi Li Wang
Keyword(s):  
Signal Transduction ◽  
P38 Mapk ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Shear Wave Elastography ◽  
Signal Transduction Pathways ◽  
Breast Lesions ◽  
Expression Levels ◽  
Tgf Β1 ◽  
Elastic Characteristics

Abstract Background: Shear wave elastography (SWE) can evaluate the tissue stiffness. Previous studies showed that the elastic characteristics of breast lesions were related to the components of extracellular matrix (ECM) which was directly or indirectly regulated by transforming growth factor beta 1(TGF-β1). However, it is rarely reported whether there is a correlation between TGF-β1 and the elastic characteristics of breast lesions. The purpose of this study was to investigate the relationship between TGF-β1 with its signal transduction pathways and the elastic characteristics of breast lesions.Methods: 135 breast lesions in 130 patients were included. Before operation or biopsy, SWE was performed. Elastic characteristics such as the maximum, mean, minimum and standard deviation (SD) of elastic modulus (Emax, Emean, Emin, Esd), the elastic ratio of the lesions to the peripheral tissue (Eratio) and the "stiff rim sign" were recorded. The expression levels of TGF-β1, Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were detected by immunohistochemistry. The elastic characteristics and the expression levels of the above-mentioned indexes of benign lesions were were analyzed.Results: Emax, Emean, Esd, Eratio, “stiff rim sign” detection rate and the expression levels of TGF- β 1, et al. of benign were lower than those of malignant lesions (P＜0.0001). The expression levels of TGF- β 1, Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were correlated with Emax, Emean, Esd, Eratio of breast lesions, the expression levels of TGF- β 1, et al. of lesions with “stiff rim sign” were higher than those of lesions without “stiff rim sign” (P＜0.05). And the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were corelated with that of TGF- β 1 (r=0.678, 0.633, 0.645, 0.611, 0.589, 0.663, P＜0.0001).Conclusions: The expression levels of TGF-β1, et al. of breast lesions were corelated with the elastic characteristics, the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were corelated with that of TGF- β 1, which speculated that TGF- β 1 might play an important role in the stiffness regulation of breast lesions through multiple signal transduction pathways.

MKP2 suppresses TGF-β1-induced epithelial-to-mesenchymal transition through JNK inhibition

2019 ◽  
Vol 133 (3) ◽  
pp. 545-550 ◽  
Author(s):  
Ivonne Loeffler
Keyword(s):  
Protein Kinase ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Renal Diseases ◽  
Line System ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein ◽  
Tgf Β1

Abstract Interstitial fibrosis is a typical feature of end-stage renal diseases, regardless of the initial cause of kidney injury. Epithelial-to-mesenchymal transition (EMT) is a mechanism that is thought to play a role in generating the interstitial matrix-producing myofibroblasts and is prominently induced by the transforming growth factor-β 1 (TGF-β1). TGF-β1 signals through a variety of Smad and non-Smad signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways. In a study published in a recent issue of Clinical Science (Clin. Sci. (2018) 132(21),2339–2355), Li et al. investigated the potential role of the Mitogen-activated protein kinase phosphatase 2 (MKP2), also known as Dusp4, in the control of EMT and renal fibrosis. Based on results obtained with an animal model of kidney fibrosis and a proximal tubular epithelial cell line system, the authors put forward a role for MKP2 as a negative feedback regulator of TGF-β1-induced EMT and fibrosis in the kidney. Intriguingly, MKP2 is found to down-regulate activity of c-Jun, but not that of other MAPKs, extracellular signal-regulated kinases or p38, implying a role for c-Jun N-terminal kinase-dependent signaling in renal fibrosis. In this commentary, I discuss the findings of Li and co-workers in the context of the recent literature placing a focus on potential clinical/therapeutic implications.

scholarly journals MEK1/2 Inhibitors Block Basal and Transforming Growth Factor β1-Stimulated JC Virus Multiplication

2007 ◽  
Vol 81 (12) ◽  
pp. 6412-6418 ◽  
Author(s):  
Veerasamy Ravichandran ◽  
Peter N. Jensen ◽  
Eugene O. Major
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Jc Virus ◽  
Transforming Growth Factor Β1 ◽  
Virus Multiplication ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Tgf Β1

ABSTRACT The multiplication of the human neurotropic polyomavirus JC virus (JCV) is regulated by cell membrane receptors and nuclear transcription factors. Signaling pathways also play a role in determining the extent to which JCV can productively infect cells. These data show that constitutively active MEK1 protein (CA-MEK1), overexpressed in cultures of human glia, supports a substantial increase in late JCV protein (Vp-1) synthesis. The specificity of this pathway was indicated by no significant enhancement of JCV multiplication through activation of other components of mitogen-activated protein kinase pathways such as p38, Jun N-terminal protein kinase, and protein kinase A. Further evidence supporting the importance of signaling in JCV infection came from addition of transforming growth factor β1 (TGF-β1), which stimulated a 200% increase of Vp-1 expression. Specific MEK1/2 inhibitors, flavenoid PD98059 and U0126, decreased the basal and TGF-β1-stimulated Vp-1 expression by 95% or more. TGF-β1 is known to phosphorylate/activate Smad DNA binding proteins that could subsequently bind or increase binding to JCV promoter sequences, linking the effects of signaling with JCV transcriptional regulation. The effectiveness with which MEK1/2 inhibitors block JCV multiplication provides insight that may contribute to development of compounds directed against JCV.

scholarly journals Transforming Growth Factor-β1 (TGF-β)–induced Apoptosis of Prostate Cancer Cells Involves Smad7-dependent Activation of p38 by TGF-β-activated Kinase 1 and Mitogen-activated Protein Kinase Kinase 3

2003 ◽  
Vol 14 (2) ◽  
pp. 529-544 ◽  
Author(s):  
Sofia Edlund ◽  
Shizhong Bu ◽  
Norbert Schuster ◽  
Pontus Aspenström ◽  
Rainer Heuchel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Tgf Β1 ◽  
Protein Kinase Kinase

The inhibitory Smad7, a direct target gene for transforming growth factor-β (TGF-β), mediates TGF-β1–induced apoptosis in several cell types. Herein, we report that apoptosis of human prostate cancer PC-3U cells induced by TGF-β1 or Smad7 overexpression is caused by a specific activation of the p38 mitogen-activated protein kinase pathway in a TGF-β–activated kinase 1 (TAK1)- and mitogen-activated protein kinase kinase 3 (MKK3)-dependent manner. Expression of dominant negative p38, dominant negative MKK3, or incubation with the p38 selective inhibitor [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole], prevented TGF-β1–induced apoptosis. The expression of Smad7 was required for TGF-β–induced activation of MKK3 and p38 kinases, and endogenous Smad7 was found to interact with phosphorylated p38 in a ligand-dependent manner. Ectopic expression of wild-type TAK1 promoted TGF-β1–induced phosphorylation of p38 and apoptosis, whereas dominant negative TAK1 reduced TGF-β1–induced phosphorylation of p38 and apoptosis. Endogenous Smad7 was found to interact with TAK1, and TAK1, MKK3, and p38 were coimmunoprecipitated with Smad7 in transiently transfected COS1 cells. Moreover, ectopically expressed Smad7 enhanced the coimmunoprecipitation of HA-MKK3 and Flag-p38, supporting the notion that Smad7 may act as a scaffolding protein and facilitate TAK1- and MKK3-mediated activation of p38.

scholarly journals The Expression of TGF-b1, p38 MAPK, and ERK-1 Protein in Cleft Affected Tissue of the Lip: An Observational Study

2021 ◽  
Vol 5 (2) ◽  
pp. 82
Author(s):  
Herman Yosef Limpat Wihastyoko ◽  
Erdo Puncak Sidarta
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Field Of View ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Affected Tissue ◽  
The Mean ◽  
Tgf Β1

Background: Cleft lip is a congenital birth defect caused by many proteins. Transforming growth factor (TGF)-β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK)-1 are proteins which regulate proliferation and apoptosis role during intrauterine period. This study aimed to observe the expression of these proteins in cleft affected tissue of the lip.Materials and Methods: A descriptive study by examining the TGF-β1, p38 MAPK, and ERK-1 immunohistochemical expression of cleft affected tissue of the lip was conducted. Subjects were patients that were participating for the social event held by Plastic Surgery Department, Faculty of Medicine, Univesitas Brawijaya, on December 3-12, 2012 in Nusa Tenggara Timur. Excess lip mucosa (waste tissue) during the operation were stored in 10% formalin then stained by immunohistochemistry for TGF-β1, p38 MAPK, and ERK-1. We counted the average protein expression under the light microscope with 1000x magnification for 20 different fields of view, randomly.Results: Paraffin blocks from 30 subjects were selected. The mean p38 MAPK expression was found to be highest, with the average of 8 per field of view; followed by the mean TGF-β1 expression, with the average of 5 per field of view; and the mean ERK-1 expression was found to be the lowest, with the average of 2 per field of view. Conclusion: Expression of p38 MAPK and TGF-β1 are higher than ERK-1, suggesting that p38 MAPK is in the same signalling pathway as TGF-β1, while ERK-1 is lower, as its role as anti-apoptotic. This is consistent with several previous studies showing that all proteins took part in the development of cleft lip or craniofacial development. Further study needs to be conducted to determine which protein plays the bigger role.Keywords: cleft lip, TGF-β1, p38 MAPK, ERK-1

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