جستجوی مقالات مرتبط با کلیدواژه « Transforming Growth Factor-? » در نشریات گروه « پزشکی »

Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-β/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl4 induced hepatic fibrosis rat model. 

This model was created through phenobarbital and CCl4 (0.2–0.35 ml/kg). Resveratrol (1 mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-β1, and PCNA in liver tissue. The TUNEL method and Masson’s Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD2, SMAD3, SMAD4, and SMAD7 expression levels were measured to determine TGF-β1 related hepatic fibrosis. 

The SMAD2, SMAD3, and SMAD4 mRNA expression levels were increased and the SMAD7 mRNA expression level was decreased in the fibrosis control group. The SMAD7 mRNA expression level was higher in the phenobarbital-CCl4 induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-β1/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells. 

Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl4 induced hepatic fibrosis.

HERV-K env is associated with several neurological disorders, including MS. Clinical studies have demonstrated a plausible interaction between HERV-K env and other MS risk factors. The present study aimed to investigate the possible association between HERV-K18 env and TGF-β. We further assessed the in vitro effect of EBV infection on HERV-K18 env expression in the presence and absence of vitamin D in MS patients.

PBMCs from 20 MS patients and 20 healthy controls were infected with the B95.8 EBV, seeded into 24-well plates and incubated in the presence or absence of 100 nM of 1,25(OH)D3. The expression levels of HERV-K18 env and TGF-β were measured using real-time PCR.

While the expression level of HERV-K18 env was significantly higher in MS patients than the healthy controls, this trend for TGF-β was significantly reverse. Interestingly, an inverse correlation was found between HERV-K18 env and TGF-β expression in MS patients, although the in vitro stimulation of PBMCs with EBV and vitamin D showed no significant differences in terms of HERV-K18 expression.

Our findings highlight the potential role of HERV-K18 env in MS patients.

Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor beta 1 (TGF-β1)-induced epithelial mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-β1.

Our study was performed at Ningbo University, Ningbo, Zhejiang, China between Mar 2017 and Jun 2018. HK-2 cells were initially treated with TGF-β1，then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTS assay and flow cytometry were employed to detect the effect of TGF-β1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 cells EMT.

Overexpressing TGF-β1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished.

TGF-β1 was a motivating factor of kidney cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-β1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti- fibrosis.

Curcumin is a plant polyphenol compound used as a traditional supplement in many countries. The potential therapeutic or preventive effects of curcumin may be related to its antioxidant and anti-inflammatory properties. The current in vitro study aimed to investigate the effect of curcumin on the expression of endothelin-1 (ET-1) stimulated by transforming growth factor-beta (TGF-β) in bovine aortic endothelial cells (BAECs). Bovine aortic endothelial cells derived from bovine aorta were maintained in low glucose DMEM (Dulbecco's modified Eagle's medium). The time-course and different concentrations of TGF-β (2 ng/mL and 10 ng/mL) were used to evaluate ET-1 mRNA expression. Also, the BAECs were treated with 10 µM of SB431542 (chemical inhibitor of TGF-β receptor) as positive control and different doses of curcumin (5 µM, 10 µM, and 15 µM). The expression of ET-1 mRNA was quantified by quantitative real-time polymerase chain reaction (qPCR). Statistical analysis was performed by one-way ANOVA with SPSS software. ET-1 mRNA expression significantly increased in six hours in the TGF-β-treated group (2.79 ± 0.9). SB431542, as well as curcumin 10 µM and 15 µM significantly decreased the expression of ET-1 mRNA by 2.3 ± 0.15, 1.5 ± 0.16, and 1.02 ± 0.01, respectively. Curcumin downregulated ET-1 mRNA; this result suggested a possible underlying molecular mechanism mediated through ET-1 to exert its anti-inflammatory and antioxidant properties.

Transforming growth factor-β (TGF-β) in addition to the C-terminal region can phosphorylate receptor-regulated Smads (R-Smads) in their linker region. The aim of the present study was to evaluate the role of signaling mediators such as NAD(P)H oxidases (reactive oxygen species [ROS] generators), ROS, and ROS-sensitive p38 mitogen-activated protein kinase (p38MAPK) in this signaling pathway in cultured human vascular smooth muscle cells (VSMCs).
The present in vitro study was performed on human VSMCs. Proteins were detected by western blotting utilizing an anti-phospho-Smad2 (Ser245/250/255) rabbit polyclonal antibody and a horseradish peroxidase-labeled secondary antibody. Glyceraldehyde-3-phosphate dehydrogenase was used as a loading control. The phospho-Smad2 linker region (pSmad2L) was detected in all the experimental groups: a control group (untreated group), a group treated with TGF-β (2 ng/mL), and a group treated with TGF-β plus different inhibitors. The data were normalized and presented as mean ± SEM. The statistical analyses were performed using SPSS, version 16.0, and the nonparametric Kruskal–Wallis test. A P value smaller than 0.05 was considered statistically significant.
The VSMCs treated with TGF-β (2 ng/mL) showed a time-dependent increase in the pSmad2L level. The highest level was observed at 15 minutes (P=0.03). The inhibitors of NAD(P) H oxidases (diphenyleneiodonium and apocynin) (P=0.04), ROS scavenger (N-acetylcysteine) (P=0.04), and p38MAPK inhibitor (SB-202190) (P=0.04) were able to reduce the increased level of the pSmad2L by TGF-β.
Our results suggested that NAD(P)H oxidases played an important role in the Smad2L phosphorylation in the human VSMCs. Furthermore, our results confirmed that ROS and p38MAPK were involved in this signaling pathway. Thus, TGF-β via a ROS-dependent mechanism can transmit its signals to the pSmad2L.

Root resorption is a complication of orthodontic treatment and till date, there is a dearth of information regarding this issue. The aim of this study was to determine whether the expression of transforming growth factor-β1 (TGF-β1, an inflammatory cytokine) is related to orthodontic force. Moreover, if associated, the expression level may be helpful in differential diagnosis, control and ultimate treatment of the disease.
In this experimental study, a total of 24 eight-week-old male Wistar rats were selected randomly. On day 0, an orthodontic appliance, which consisted of a closed coil spring, was ligated to the upper right first molar and incisor. The upper left first molar in these animals was not placed under orthodontic force, thus serving as the control group. On day 21, after anesthesia, the animals were sacrificed. The rats were then divided into two equal groups where the first group was subjected to histological evaluation and the second group to reverse transcriptase-polymerase chain reaction (RT-PCR). Orthodontic tooth movement was measured in both groups to determine the influence of the applied force.
Statistical analysis of data showed a significant root resorption between the experimental group and control group (P Based on the findings of this study, we suggest that there is a direct relationship between orthodontic force and orthodontic induced inflammatory root resorption. In addition, no relationship is likely to exist between root resorption and TGF-β1 expression in the resorptive lacunae.

Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS.
A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests.
A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86).
This meta-analysis showed that TGF-β1-509C/T gene polymorphism no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings.

Natural biomaterials and growth factors are key factors in tissue engineering. The objective of the present study was to evaluate transforming growth factor beta 1 (TGF-β1) and curcumin on proliferation and differentiation of nasal-derived chondrocyte seeded on the fibrin glue scaffold.
Chondrocytes were isolated from nasal samples. Nasal-derived chondrocytes were seeded on fibrin glue at chondrogenic induction medium for 2 weeks. In this study, the effects of various concentrations of curcumin and TGF-β1 on the survival and proliferation of chondrocytes seeded on fibrin biomaterial were assessed by MTT assays. Also, chondrocytespecific gene expression was assessed by real-time polymerase chain reaction (PCR).
There were significant differences among the group treated with curcumin 10 μg compared to other groups with regard to cell viability. Also, gene expression of collagen type II, aggrecan, and SOX9 in the chondrocytes seeded on fibrin biomaterial containing the growth factor TGF-β1 significantly differed from those of curcumin and control group.
Our results indicate that TGF-β1 and natural biomaterial of curcumin can be used effectively in chondrogenic viability and differentiation of nasal-derived chondrocyte.

Context: Cleft palate is the second most common birth defect and is considered as a challenge for pediatric plastic surgeons. There is still a general lack of a standard protocol and patients often require multiple surgical interventions during their lifetime along with disappointing results.Evidence Acquisition: PubMed search was undertaken using search terms including 'cleft palate repair', 'palatal cleft closure', 'cleft palate + stem cells', 'cleft palate + plasma rich platelet', 'cleft palate + scaffold', 'palatal tissue engineering', and 'bone tissue engineering'. The found articles were included if they defined a therapeutic strategy and/or assessed a new technique. We reported a summary of the key-points concerning cleft palate development, the genes involving this defect, current therapeutic strategies, recently novel aspects, and future advances in treatments for easy and fast understanding of the concepts, rather than a systematic review. In addition, the results were integrated with our recent experience. Tissue engineering may open a new window in cleft palate reconstruction. Stem cells and growth factors play key roles in this field.

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa which is considered by the World Health Organization (WHO) as a premalignant condition. One step in malignant development is so called epithelial mesenchymal transition (EMT), a process whereby epithelial cells acquire mesenchymal characteristics. A factor known to induce EMT is the transforming growth factor-β (TGF-β), which uses the Smad proteins as mediators for its signaling. The aim of this study was to compare the expression of Smad 3 in Oral Lichen Planus and normal oral mucosa. This descriptive analytic study was performed on 30 patients with OLP (21 women and 9 men with mean age of 45.23± 2.44 years) and 20 normal oral mucosa (14 women and 6 men with mean age of 46.95± 2.21 years). The samples were studied by immunohistochemical staining. Data were analyzed with paired T-test and Wilcoxon test by SPSS software. Expression of Smad3 in OLP samples and normal oral mucosa was different. This difference was statistically significant (P<0.001). The apparently higher expression of Smad 3 in oral lichen planus compared to normal oral mucosa might help to discuss its higher potential for malignant transition.