Protective Effects of Transforming Growth Factor-β1 Knockdown in Human Umbilical Cord Mesenchymal Stem Cells against Subarachnoid Hemorrhage in a Rat Model

2020 ◽  
Vol 49 (1) ◽  
pp. 79-87
Author(s):  
Hongwei Chen ◽  
Li Chen ◽  
Dongcheng Xie ◽  
Jianxing Niu
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Growth Factor ◽  
Beneficial Effect ◽  
Umbilical Cord ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Umbilical Cord ◽  
Chronic Hydrocephalus ◽  
Tgf Β1

Background: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-β1 (TGF-β1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-β1 knockdown on chronic hydrocephalus after SAH. Methods: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-β1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-β1, p-Smad2/3, and Smad2/3 were measured using western blotting. Results: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-β1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-β1 knockdown. Conclusion: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-β1/Smad2/3 signaling pathway. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects.

Platelet-Rich Plasma Powder: A New Preparation Method for the Standardization of Growth Factor Concentrations

2016 ◽  
Vol 45 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Matthias Kieb ◽  
Frank Sander ◽  
Cornelia Prinz ◽  
Stefanie Adam ◽  
Anett Mau-Möller ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Clinical Application ◽  
Whole Blood ◽  
Sports Medicine ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tgf Β1

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.

scholarly journals Manipulation of the Fascial System Applied During Acute Inflammation of the Connective Tissue of the Thoracolumbar Region Affects Transforming Growth Factor-β1 and Interleukin-4 Levels: Experimental Study in Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Maria Elisa Duarte França ◽  
Larissa Sinhorim ◽  
Daniel Fernandes Martins ◽  
Robert Schleip ◽  
Nicolas A. M. M. Machado-Pereira ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Transforming Growth Factor ◽  
Neutrophil Migration ◽  
Transforming Growth Factor Β1 ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Monocyte Chemoattractant Protein 1 ◽  
Thoracolumbar Region ◽  
Tgf Β1

Fascia can become rigid and assume a fibrotic pattern due to inflammatory processes. Manipulation of the fascial system (MFS), manual technique targeting connective tissues, is commonly used in clinical practice in pain management. We aimed to verify MFS effects on the connective tissue inflammatory changes in mice. Swiss Mus musculus male mice (n = 44) were distributed into groups: carrageenan without treatment (Car, n = 11), carrageenan with MFS (Car + MFS, n = 12), saline without treatment (n = 10), and saline with MFS (saline + MFS, n = 11). Interleukin 4 (IL-4), IL-6, tumor necrosis factor (TNF), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein 1 (MCP-1) levels were verified by enzyme-linked immunosorbent assay. Neutrophil (Ly-6G), macrophage (F4/80), and nitric oxide synthase 2 (NOS-2) were identified using Western blot. The MFS protocol was applied from the first to the third day after inflammation of the connective tissue of the thoracolumbar region. There was a significant MFS effect on IL-4 (p = 0.02) and TGF-β1 (p = 0.04), without increasing MCP-1, TNF, and IL-6 levels (p > 0.05) on thoracolumbar region from Car + MFS, in comparison with saline. Ly-6G in Car + MFS presented lower levels when compared with saline (p = 0.003) or saline + MFS (0.003). NOS-2 levels were lower in Car + MFS than in saline + MFS (p = 0.0195) or saline (p = 0.003). MFS may have an anti-inflammatory effect, based on TGF-β1 and IL-4. IL-4 may have inhibited neutrophil migration. Lower levels of NOS-2 may be linked to the lack of macrophages, which are responsible for NOS-2 expression.

scholarly journals Different effects of soybean isoflavone genistein on transforming growth factor levels during orthodontic tooth movement among young and old rabbits

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 2074
Author(s):  
Verastuti Indriasari ◽  
Sri Suparwitri ◽  
Christnawati Christnawati ◽  
Ananto Ali Alhasyimi
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bone Apposition ◽  
Standard Curve ◽  
Tgf Β1

Background: Orthodontic treatment to improve aesthetics and for health reasons is performed in children and adults. Elderly individuals have low levels of estrogen, this results in alveolar bone resorption being greater than alveolar bone apposition. Isoflavones present in soybeans may be able to improve the remodeling process through the induction of osteoblastogenesis by increasing transforming growth factor-β1 (TGF-β1) levels. This study aimed to assess the comparative effect of soybean genistein isoflavone to TGF-β1 during orthodontic tooth movement among juvenile and adult rabbits. Methods: In this study, 12 healthy female rabbits were used. Subjects were divided into four groups (n=3); YG group (young rabbits), YGI group (young rabbits + isoflavones genistein), OG group (old rabbits), and OGI group (old rabbits + isoflavones genistein). Two lower incisors of the rabbit were moved distally using an orthodontic force (50 grams force) delivered by an open coil spring, which was inserted between two brackets. During active movements, the genistein isoflavones were given from the initial installation of the device until days 21, at a dose of 1.2 mg/kg BW once a day. Measurement of TGF-β levels were performed on days 1, 7, 14, 21 after appliance installation. TGF-β1 expression was analyzed using enzyme-linked immunosorbent assay (ELISA) and the optical density (OD) of the sample quantifed using a standard curve. The data obtained were analyzed using one-way Anova followed by Tukey HSD test. Results: The TGF-β1 levels were found to highest in the YGI group, and the TGF-β levels were significantly lower in the OG group (p<0.05). ELISA analysis also revealed that TGF-β1 levels of the OGI group were significantly higher when compared with the OG group (p<0.05). Conclusion: The administration of soybean genistein isoflavones could improve TGF-β1 levels in old rabbit’s during active orthodontic tooth movement.

scholarly journals RANSFORMING GROWTH FACTOR-β1 IN PATIENTS WITH BRONCHIAL ASTHMA: PATHOGENETIC, CLINICAL AND THERAPEUTIC ASPECTS (LITERATURE REWIEW AND OWN RESULTS)

2021 ◽  
Vol 2021 (2) ◽  
pp. 34-42
Author(s):  
V. V. Kachkovska ◽  
A. V. Kovchun ◽  
A. M. Bondarkova ◽  
L. N. Prystupa
Keyword(s):  
Growth Factor ◽  
Bronchial Asthma ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Key Words Bronchial Asthma ◽  
Tgf Β1

The goal of our research was to analyze the role of transforming growth factor-β1 (TGF-β1 ) in airway remodeling, inflammation, clinical course, treatment efficacy in patients with bronchial asthma (BA) according to the literature data, as well as determination of this biomarkers level in the blood of BA patients. Material and research methods. The publications is containing the results of studies on the role of TGF-β1 in the course of BA have been analyzed. The level of TGF-β1 in the blood was determined within enzyme-linked immunosorbent assay using kits “IBL International GMBH, Germany” in 553 BA patients and in 95 healthy individuals. Results. The article presents data about TGF-β1 influence on the processes of airway remodeling in BA patients, its role in microcirculation disorders, mucus production, eosinophilic inflammation and severity of clinical symptoms of the disease. The level of TGF-β1 expression was associated with disease control, severity and duration of the disease, despite conflicting data that require further study. In addition, there were presented recent research data about TGF-β1 as a marker of airway remodeling and as a therapeutic target in the treatment of BA patients. Glucocorticoids, tiotropium bromide, methylxanthines, selective inhibitors of TGF-β1 , resveratrol, simvastatin and montelukast and their mechanisms of influence were presented in detail. Significantly higher level of TGF-β1 in the blood of patients with BA was found (38.5 ± 0.7) pg/ml compared with healthy individuals (33.9 ± 1.0) pg /ml, p = 0.007. Conclusion. A significantly higher level of TGF-β1 was revealed in the blood of BA patients. In our opinion, a differentiated analysis of the content of this marker depending on the phenotype of the disease is important, which would explain the conflicting results of different studies, deepen understanding of its pathophysiological and clinical role in order to develop methods for slowing airway remodeling. Key words: bronchial asthma, transforming growth factor-β1 (TGF-β1), airway remodeling.

scholarly journals Effects of Transforming Growth Factor-β1 on Renal Extracellular Matrix Components and Their Regulating Proteins

1999 ◽  
Vol 10 (10) ◽  
pp. 2109-2119 ◽  
Author(s):  
JULIE A. DOUTHWAITE ◽  
TIMOTHY S. JOHNSON ◽  
JOHN L. HAYLOR ◽  
PHIL WATSON ◽  
A. MEGUID EL NAHAS
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Tissue Transglutaminase ◽  
Rat Kidney ◽  
Transforming Growth Factor Β1 ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Extracellular Matrix Components ◽  
Tgf Β1

Abstract. Transforming growth factor-β1 (TGF-β1) is widely regarded as a potent fibrogenic renal growth factor. In cell culture, TGF-β1 has been shown to increase various extracellular matrix (ECM) proteins and tissue inhibitors of metalloproteinases (TIMP), while decreasing matrix metalloproteinases (MMP), providing the optimum environment for progressive ECM accumulation. This study, which uses the isolated perfused rat kidney (IPRK), describes for the first time in a whole kidney preparation the action of TGF-β1 on factors associated with ECM processing. This model allows the study of the intact rat kidney with physiologic cell-cell interactions in the absence of confounding systemic influences. Left kidneys were removed from male Wistar rats by a nonischemic technique and perfused with a sterile, apyrogenic, endotoxin-free perfusate, based on the plasma volume expander Hemaccel (polygeline), at constant pressure in a recirculating IPRK system. Kidneys were perfused for 1 h either with (n = 3) or without (n = 3) recombinant human TGF-β1 (20 ng/ml). The effects of perfusion were controlled by comparison with the nonperfused contralateral kidney (n = 6). TGF-β1 was measured in the perfusate and urine, at the start and end of the experiment using an enzyme-linked immunosorbent assay to its biologically active form. After perfusion, sections of the kidneys were analyzed for changes in mRNA by Northern blotting. Significant increases in mRNA for fibronectin (7.5-fold, P < 0.01), heparan sulfate proteoglycan core protein (53-fold, P < 0.001), laminin β1 (12-fold, P < 0.001), collagen α1(IV) (17-fold, P < 0.001), collagen α1(III) (fourfold, P < 0.001), and MMP9 (twofold, P < 0.05) were observed after perfusion with TGF-β1. Measurement of TIMP1, TIMP2, TIMP3, MMP1, and MMP2 mRNA demonstrated no detectable change, whereas determination of mRNA for tissue transglutaminase, an enzyme capable of cross-linking many ECM components, showed an eightfold increase (P < 0.01). This study suggests that in the IPRK and in the absence of other exogenous growth factors, TGF-β1 selectively increases the synthesis of ECM and tissue transglutaminase without changes that would result in the reduction of ECM degradation.

scholarly journals Different effects of soybean isoflavone genistein on transforming growth factor levels during orthodontic tooth movement among young and old rabbits

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2074 ◽  
Author(s):  
Verastuti Indriasari ◽  
Sri Suparwitri ◽  
Christnawati Christnawati ◽  
Ananto Ali Alhasyimi
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bone Apposition ◽  
Standard Curve ◽  
Tgf Β1

Background: Orthodontic treatment to improve aesthetics and for health reasons is performed in children and adults. Elderly individuals have low levels of estrogen, this results in alveolar bone resorption being greater than alveolar bone apposition. Isoflavones present in soybeans may be able to improve the remodeling process through the induction of osteoblastogenesis by increasing transforming growth factor-β1 (TGF-β1) levels. This study aimed to assess the comparative effect of soybean genistein isoflavone to TGF-β1 during orthodontic tooth movement among juvenile and adult rabbits. Methods: In this study, 12 healthy female rabbits were used. Subjects were divided into four groups (n=3); YG group (young rabbits), YGI group (young rabbits + isoflavones genistein), OG group (old rabbits), and OGI group (old rabbits + isoflavones genistein). Two lower incisors of the rabbit were moved distally using an orthodontic force (50 grams force) delivered by an open coil spring, which was inserted between two brackets. During active movements, the genistein isoflavones were given from the initial installation of the device until days 21, at a dose of 1.2 mg/kg BW once a day. Measurement of TGF-β levels were performed on days 1, 7, 14, 21 after appliance installation. TGF-β1 expression was analyzed using enzyme-linked immunosorbent assay (ELISA) and the optical density (OD) of the sample quantifed using a standard curve. The data obtained were analyzed using one-way Anova followed by Tukey HSD test. Results: The TGF-β1 levels were found to highest in the YGI group, and the TGF-β levels were significantly lower in the OG group (p<0.05). ELISA analysis also revealed that TGF-β1 levels of the OGI group were significantly higher when compared with the OG group (p<0.05). Conclusion: The administration of soybean genistein isoflavones could improve TGF-β1 levels in old rabbit’s during active orthodontic tooth movement.

scholarly journals Effect of coagulation time on the concentration of epitheliotrophic components of autologous serum.

2020 ◽  
Author(s):  
Ana Miguel-Camacho ◽  
Karla García-Guillén ◽  
Marcelino Aguirre-Garza ◽  
Rafael BR León-Cachón ◽  
Francisco Amparo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Autologous Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Coagulation Time ◽  
Cross Sectional ◽  
Significant Difference ◽  
Tgf Β1

Abstract Background: To know the influence of coagulation time on the concentration of epitheliotropic factors of autologous serum.Methods: A prospective, cross-sectional and experimental study was conducted evaluating the concentrations of epitheliotropic factors in the serum of 20 healthy volunteers over 18 years of age, who did not suffer from diseases or took any medication or with a history of blood transfusion in the last year, those with diagnosis of anemia, coagulation diseases or another situation that contraindicates the sampling were excluded. Epidermal growth factor (EGF), Transforming growth factor β1 (TGF-β1) and Fibronectin were quantified in the various undiluted serum samples by an enzyme-linked immunosorbent assay.Results: 65% were male with an average age of 22.7 ± 5.47 years (range 19 to 45 years). Age was similar in both groups (p = 0.87), men had an average age of 22.85 ± 6.84 years and women 22.43 ± 1.13 years. Vitamin A and Fibronectin did not have a statistically significant difference of concentration at 2 and 24 hours, while the concentration of TGF-β1 had a statistically significant decrease as the clot formation time increased (average 0.22 range, 0.003,0.451), opposite, the EGF increased its concentration statistically significantly with the longer coagulation time (average -0.39 range, -0.60, -0.18).Conclusions: a prolonged clotting time (24 hours) have a significant impact on the composition and epitheliotrophic factors of the serum, increasing the EGF concentrations, and lowering the TGF-β1.

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.

Sign in / Sign up

Export Citation Format

Share Document