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.

scholarly journals The Role of TGFβ in Clinical Cancer Response

2020 ◽  
pp. 1-8
Author(s):  
John Nemunaitis ◽  
Cassidy Gillman ◽  
John Nemunaitis ◽  
Justin Creeden ◽  
Lance Dworkin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Clinical Intervention ◽  
Immune Checkpoint Blockade ◽  
Signaling Networks ◽  
Signal Transduction Pathways ◽  
Molecule Inhibitor ◽  
Growth Factor Beta

The role of transforming growth factor beta (TGFβ) is context dependent. Even within the specific context of cancer, the functional significance of TGFβ varies according to environmental conditions. Therapies targeting TGFβ capitalize upon recent discoveries in canonical SMAD-dependent biochemical signaling networks as well as non-canonical SMAD-independent biochemical signal transduction pathways and mechanobiological signal transduction pathways. TGFβ clinical trials utilizing vaccine, small molecule inhibitor, antibody, and aptamer strategies support TGFβ as a viable anticancer target for a variety of cancer diagnoses. Combination therapies incorporating TGFβ inhibition and immune checkpoint blockade provide additional avenues for future TGFβ-based clinical intervention.

LncRNA HOTAIR promotes endometrial fibrosis by activating TGF-β1/Smad pathway

2020 ◽  
Vol 52 (12) ◽  
pp. 1337-1347
Author(s):  
Jianhong Wu ◽  
Lingge Jin ◽  
Yudi Zhang ◽  
Aihong Duan ◽  
Juhong Liu ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Quantitative Polymerase Chain Reaction ◽  
Endometrial Stromal Cells ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Abstract Homeobox transcript antisense RNA (HOTAIR) is a long non-coding RNA associated with a number of fibrosis-related diseases. The aim of this study was to investigate the specific role of HOTAIR in the development of endometrial fibrosis and to identify the molecular mechanisms underlying this process. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of HOTAIR in samples of intrauterine adhesion (IUA) tissue and in endometrial stromal cells (ESCs) that had been treated with transforming growth factor beta 1 (TGF-β1). Additionally, we transfected ESCs with either overexpression plasmid (pcDNA-HOTAIR) or silencing construct (si-HOTAIR) and then treated these cells with TGF-β1. We then performed RT-qPCR and western blot analysis, along with cell proliferation and apoptosis assays, to investigate the effects of HOTAIR on the transdifferentiation of ESCs into myofibroblasts. The results showed that the expression levels of HOTAIR were significantly elevated in IUA tissue and in ESCs that had been treated with TGF-β1. The overexpression of HOTAIR had a pro-fibrotic effect on ESCs, while the silencing of HOTAIR exerted an anti-fibrotic effect. Most importantly, the protein expression levels of p-Smad2 and p-Smad3 were significantly upregulated in TGF-β1-treated ESCs transfected with pcDNA-HOTAIR and were downregulated after transfection with si-HOTAIR constructs. These data indicate that HOTAIR promotes endometrial fibrosis by activating the TGF-β1/Smad signaling pathway, suggesting that the inhibition of HOTAIR may represent a promising therapeutic option for suppressing endometrial fibrosis.

scholarly journals THE EFFECT OF ALPHA-MANGOSTIN ON TRANSFORMING GROWTH FACTOR BETA 1 (TGF-β1) AND MATRIX METALLOPROTEINASE-3 EXPRESSION IN TGF-β-INDUCED HEPATIC STELLATE CELLS

2019 ◽  
pp. 177-180
Author(s):  
SYARINTA ADENINA ◽  
RAHMANIAH RAHMANIAH ◽  
YUYUNTIA YUYUNTIA ◽  
VIVIAN SOETIKNO ◽  
MELVA LOUISA
Keyword(s):  
Matrix Metalloproteinase ◽  
Transforming Growth Factor Beta ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Trypan Blue Exclusion Method ◽  
Expression Levels ◽  
Matrix Metalloproteinase 3 ◽  
Β Receptor ◽  
Tgf Β1

Objective: Alpha-mangostin (α-MG) has been shown to possess antifibrotic effects. However, the specific mechanism of action of this compoundremains poorly understood. Therefore, the aim of this study was to investigate the effect of α-MG on the expression levels of transforming growthfactor (TGF)-β1 and matrix metalloproteinase-3 (MMP3) in hepatic stellate cells (HSCs) induced by TGF-β.Methods: Immortalized HSCs and LX-2 cells were incubated with TGF-β with or without α-MG (5 and 10 μM). The viability of LX-2 cells was assessedusing the Trypan Blue Exclusion Method. The effect of α-MG on cell morphology and the mRNA expression levels of TGF-β1, TGF-β receptor, and MMP3was then evaluated.Results: TGF-β enhanced the proliferation of HSCs and caused significant increases in the expression levels of TGF-β1, TGF-β receptor, and MMP3.α-MG treatment reduced the proliferation of HSCs and decreased the expression levels of TGF-β1, TGF-β1 receptor, and MMP3.Conclusion: α-MG is a potential antifibrotic agent due to its antiproliferative and antifibrogenic effects, mainly by suppressing the expression of TGF-βand MMP3 on the surfaces of activated HSCs.

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 Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Manal G. Mahmoud ◽  
Mohsen S. Asker ◽  
Mohamed E. El Awady ◽  
Amal I. Hassan ◽  
Nadia A. R. Zaharan ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Periodate Oxidation ◽  
Hepatic Tissue ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Glutamyl Transferase ◽  
Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model

2021 ◽  
pp. 036354652110285
Author(s):  
Jong Pil Yoon ◽  
Hun-Min Kim ◽  
Jin-Hyun Choi ◽  
Hae Rim Kang ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Rat Model ◽  
Transforming Growth Factor Beta ◽  
Rotator Cuff Repair ◽  
Animal Experiment ◽  
Transforming Growth Factor ◽  
Group 3 ◽  
Growth Factor Beta ◽  
Cuff Repair ◽  
Tgf Β1

Background: The healing failure rate after rotator cuff repair is considerably high. Purpose: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-β1) on the sustained release of TGF-β1 and rotator cuff healing in a rat model. Study Design: Controlled laboratory study. Methods: A porous suture was developed, and its tensile strength was measured. TGF-β1 was delivered using the porous suture, and a TGF-β1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-β1; and group 3, repair using the porous suture containing TGF-β1. Eight weeks after repair, biomechanical and histological analyses were performed. Results: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-β1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). Conclusion: The porous suture containing TGF-β1 could sustainedly and safely release TGF-β1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. Clinical Relevance: The porous suture containing TGF-β1 might improve healing after rotator cuff repair.

Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

2021 ◽  
pp. 096032712110084
Author(s):  
AM Kabel ◽  
HH Arab ◽  
MA Abd Elmaaboud
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Liver Function Tests ◽  
Toll Like Receptor ◽  
Caspase 9 ◽  
Toll Like Receptor 4 ◽  
Growth Factor Beta ◽  
Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

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