scholarly journals The Effect of Curcumin on Regression of Liver Fibrosis through Decreased Expression of Transforming Growth Factor-β1 (TGF-β1)

2019 ◽  
Vol 11 (1) ◽  
pp. 52-8 ◽  
Author(s):  
Supriono Supriono ◽  
Asri Nugraheni ◽  
Handono Kalim ◽  
Mudjiwijono Handaru Eko
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Tissue ◽  
Transforming Growth Factor ◽  
Positive Control ◽  
Negative Control ◽  
Control Groups ◽  
Treatment Groups ◽  
Tgf Β1

BACKGROUND: Transforming growth factor (TGF)-β1 has a pivotal role in liver fibrogenesis. Curcumin effectively prevent the progression of liver fibrosis through inhibition of TGF-β1/Sma and drosophila MAD (Smad) signaling pathway. However, the role of curcumin in the regression of liver fibrosis is still unknown. This study investigated the role of curcumin and TGF-β1 in liver fibrosis regression.METHODS: An experimental Wistar rat model included 6 treatment groups as well as positive and negative control groups. The treatment and positive control groups were injected with carbon tetrachlorid (CCl4) for 9 weeks to induce liver fibrosis. After cessation of injection, 3 of the treatment groups were given curcumin and 3 were given carboxymethylcellulose (CMC) for 2, 5 and 9 weeks, while the positive control was untreated. The negative control was injected with normal saline. TGF-β1 liver tissue levels were analyzed by ELISA, while the TGF-β1 expression in liver cells was analyzed by immunohistochemical assay. The metavir score was used to assess the degree of liver fibrosis. Values of p<0.05 were regarded as statistically significant.RESULTS: Nine weeks of CCl4 injection induced liver fibrosis (metavir F3); and significantly increased TGF-β1 levels and expression in tissues (p=0.00, p=0.021, respectively). Curcumin administration decreased levels and expression of TGF-β1 in the liver and accelerated regression of liver fibrosis. There was a significant correlation between duration of administration of curcumin with an expression of TGF-β1 in the liver tissue (r=0.87; p<0.00).CONCLUSION: Curcumin accelerates regression of liver fibrosis, likely through decreasing of TGF-β1 expression in the liver.KEYWORDS: curcumin, TGF-β1, liver fibrosis regression, CCl4, animal model

scholarly journals Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jonghwa Kim ◽  
Wonseok Kang ◽  
So Hee Kang ◽  
Su Hyun Park ◽  
Ji Young Kim ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tyrosine Kinase ◽  
Focal Adhesion ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Type I ◽  
Tyrosine Kinase 2 ◽  
The Impact ◽  
Tgf Β1

AbstractHepatic fibrogenesis is characterized by activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix (ECM). The impact of ECM on TGF-β-mediated fibrogenic signaling pathway in HSCs has remained obscure. We studied the role of non-receptor tyrosine kinase focal adhesion kinase (FAK) family members in TGF-β-signaling in HSCs. We used a CCl4-induced liver fibrosis mice model to evaluate the effect of FAK family kinase inhibitors on liver fibrosis. RT-PCR and Western blot were used to measure the expression of its target genes; α-SMA, collagen, Nox4, TGF-β1, Smad7, and CTGF. Pharmacological inhibitors, siRNA-mediated knock-down, and plasmid-based overexpression were adopted to modulate the function and the expression level of proteins. Association of PYK2 activation with liver fibrosis was confirmed in liver samples from CCl4-treated mice and patients with significant fibrosis or cirrhosis. TGF-β treatment up-regulated expression of α-SMA, type I collagen, NOX4, CTGF, TGF-β1, and Smad7 in LX-2 cells. Inhibition of FAK family members suppressed TGF-β-mediated fibrogenic signaling. SiRNA experiments demonstrated that TGF-β1 and Smad7 were upregulated via Smad-dependent pathway through FAK activation. In addition, CTGF induction was Smad-independent and PYK2-dependent. Furthermore, RhoA activation was essential for TGF-β-mediated CTGF induction, evidenced by using ROCK inhibitor and dominant negative RhoA expression. We identified that TGF-β1-induced activation of PYK2-Src-RhoA triad leads to YAP/TAZ activation for CTGF induction in liver fibrosis. These findings provide new insights into the role of focal adhesion molecules in liver fibrogenesis, and targeting PYK2 may be an attractive target for developing novel therapeutic strategies for the treatment of liver fibrosis.

scholarly journals The role of TGF-β2 in cartilage development and diseases

2021 ◽  
Vol 10 (8) ◽  
pp. 474-487
Author(s):  
Mengmeng Duan ◽  
Qingxuan Wang ◽  
Yang Liu ◽  
Jing Xie
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Vital Role ◽  
Cartilage Defects ◽  
Cartilage Development ◽  
Physiological Processes ◽  
Cartilage Diseases ◽  
Autologous Mesenchymal Stem Cells ◽  
Tgf Β1

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.

Abstract 17285: A Selective Transforming Growth Factor-β and Growth Differentiation Factor-15 Ligand Trap Attenuates Pulmonary Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lai-Ming Yung ◽  
Samuel D Paskin-Flerlage ◽  
Ivana Nikolic ◽  
Scott Pearsall ◽  
Ravindra Kumar ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Rna Seq ◽  
Differentiation Factor ◽  
Group I ◽  
Tgf Β1

Introduction: Excessive Transforming Growth Factor-β (TGF-β) signaling has been implicated in pulmonary arterial hypertension (PAH), based on activation of TGF-β effectors and transcriptional targets in affected lungs and the ability of TGF-β type I receptor (ALK5) inhibitors to improve experimental PAH. However, clinical use of ALK5 inhibitors has been limited by cardiovascular toxicity. Hypothesis: We tested whether or not selective blockade of TGF-β and Growth Differentiation Factor (GDF) ligands using a recombinant TGFβ type II receptor extracellular domain Fc fusion protein (TGFBRII-Fc) could impact experimental PAH. Methods: Male SD rats were injected with monocrotaline (MCT) and received vehicle or TGFBRII-Fc (15 mg/kg, twice per week, i.p.). C57BL/6 mice were treated with SU-5416 and hypoxia (SUGEN-HX) and received vehicle or TGFBRII-Fc. RNA-Seq was used to profile transcriptional changes in lungs of MCT rats. Circulating levels of GDF-15 were measured in 241 PAH patients and 41 healthy controls. Human pulmonary artery smooth muscle cells were used to examine signaling in vitro . Results: TGFBRII-Fc is a selective ligand trap, inhibiting the ability of GDF-15, TGF-β1, TGF-β3, but not TGF-β2 to activate SMAD2/3 in vitro . In MCT rats, prophylactic treatment with TGFBRII-Fc normalized expression of TGF-β transcriptional target PAI-1, attenuated PAH and vascular remodeling. Delayed administration of TGFBRII-Fc in rats with established PAH at 2.5 weeks led to improved survival, decreased PAH and remodeling at 5 weeks. Similar findings were observed in SUGEN-HX mice. No valvular abnormalities were found with TGFBRII-Fc treatment. RNA-Seq revealed GDF-15 to be the most highly upregulated TGF-β ligand in the lungs of MCT rats, with only modest increases in TGF-β1 and no change in TGF-β2/3 observed, suggesting a dominant role of GDF-15 in the pathophysiology of this model. Plasma levels of GDF-15 were significantly increased in patients with diverse etiologies of WHO Group I PAH. Conclusions: These findings demonstrate that a selective TGF-β/GDF-15 trap attenuates experimental PAH, remodeling and mortality, without causing valvulopathy. These data highlight the potential role of GDF-15 as a pathogenic molecule and therapeutic target in PAH.

scholarly journals Evidence for a Role of Transforming Growth Factor (TGF)-β1 in the Induction of Postglomerular Albuminuria in Diabetic Nephropathy

Diabetes ◽  
2007 ◽  
Vol 56 (2) ◽  
pp. 380-388 ◽  
Author(s):  
Leileata M. Russo ◽  
Elisabetta del Re ◽  
Dennis Brown ◽  
Herbert Y. Lin
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Tgf Β1

scholarly journals Osteoprotegerin expression in liver is induced by IL-13 through TGF-β

2020 ◽  
Author(s):  
Adhyatmika Adhyatmika ◽  
Kurnia SS Putri ◽  
Emilia Gore ◽  
Keri Mangnus ◽  
Catharina Reker-Smit ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Tissue ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Experimental Models ◽  
Wild Type ◽  
3T3 Fibroblasts ◽  
Liver Slices ◽  
Deficient Mice

Backgrounds: Osteoprotegerin (OPG) is a profibrotic mediator produced by myofibroblasts under influence of transforming growth factor β (TGFβ). Its expression in experimental models of liver fibrosis correlates well with disease severity and treatment responses. The regulation of OPG in liver tissue is largely unknown and we therefore set out to elucidate which growth factors/interleukins associated with fibrosis induce OPG and through which pathways. Methods: Precision-cut liver slices of wild type and STAT6-deficient mice and 3T3 fibroblasts were used to investigate the effects of TGFβ, interleukin (IL) 13 (IL13), IL1β, and platelet-derived growth factor BB (PDGF-BB) on expression of OPG. Results: In addition to TGFβ, only IL13 and not PDGF-BB or IL1β could induce OPG expression in 3T3 fibroblasts and liver slices. This IL13-dependent induction was not shown in liver slices of STAT6-deficient mice and when wild type slices were cotreated with TGFβ receptor 1 kinase inhibitor galunisertib, STAT6 inhibitor AS1517499, or AP1 inhibitor T5224. This suggests that the OPG-inducing effect of IL13 is mediated through IL13 receptor α1-activation and subsequent STAT6-dependent upregulation of IL13 receptor α2, which in turn activates AP1 and induces production of TGFβ and subsequent production of OPG. Conclusion: We have shown that IL13 induces OPG release by liver tissue through a TGFβ-dependent pathway involving both the α1 and the α2 receptor of IL13 and transcription factors STAT6 and AP1. OPG may therefore be a novel target for the treatment liver fibrosis as it is mechanistically linked to two important regulators of fibrosis in liver, namely IL13 and TGFβ1.

scholarly journals IN VIVO EFFICACY OF TOPICAL BINAHONG (ANREDERA CORDIFOLIA (TEN.) STEENIS) LEAF ETHANOLIC EXTRACT ON TRANSFORMING GROWTH FACTOR-BETA 1 IN INFECTED WOUNDS

2021 ◽  
pp. 99-102
Author(s):  
RIZKI ANDINI NAWAWI ◽  
MUHAMMAD TOTONG KAMALUDDIN ◽  
THEODORUS
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ethanolic Extract ◽  
Bacterial Count ◽  
Treatment Groups ◽  
Infected Wounds ◽  
Growth Factor Beta ◽  
Tgf Β1

Objective: This study’s aim was to assess the efficacy of topical Binahong (Anredera cordifolia (Ten.) Steenis) leaf ethanolic extract administration on serum transforming growth factor-beta 1 (TGF-β1) in infected wounds. Methods: An experimental study, in vivo, was conducted in the Biotechnology Laboratory and Animal House, Faculty of Medicine, Universitas Sriwijaya, Palembang, from July to September 2020. There were 30 male Wistar rats aged 10–12 weeks with excisional wounds infected with Staphylococcus aureus ATCC 25923. The rats were divided into five groups and received three concentrations of Binahong leaf extracts (2.5%, 5%, and 10%), salve base, and povidone iodine 10% topically twice daily for 14 days. Serum was obtained before treatment and after 14 days of treatment. Wound area and bacterial count were also recorded and analyzed. Data analysis was performed using computer software. Results: Wound size and bacterial count were significantly decreased in treatment groups receiving topical Binahong leaf ethanolic extract. No significant increase in serum TGF-β1 was observed in all treatment groups. Conclusion: Topical administration of Binahong leaf ethanolic extract on rats with infected wounds for 14 days did not significantly increase serum TGF-β1.

scholarly journals ROLE OF HUMAN DISKOIDIN DOMAIN RECEPTOR 1 IN THE PROGRESSION OF CHRONIC PYELONEPHRITIS IN CHILDREN

2017 ◽  
pp. 5-20
Author(s):  
N. N. Kaladze ◽  
E. I. Slobodyan
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Inverse Correlation ◽  
Chronic Pyelonephritis ◽  
Clinical Form ◽  
Discoidin Domain Receptors ◽  
Collagen Receptors ◽  
Mediators Of Inflammation ◽  
Tgf Β1

The purpose: to evaluate the role of collagen receptors Human Discoidin Domain Receptors (DDR1) as mediators of inflammation, proliferation and fibrosis in children with chronic pyelonephritis (CP), to reveal their relationship to the clinical form of the disease and the characteristics of its flow. Materials and methods: The levels of DDR1, transforming growth factor (TGF-β1), insulin-like growth factor (IGF-1) in the serum, β2 - microglobulin ( β2- MG) in the serum and urine were identified during the study of 40 children, ages 6 to 16 with CP in a state of clinical and laboratory remission. Results: Clinical and laboratory remission HP was associated with significant increased levels of DDR1 sera from long ill patients with frequent exacerbations, as well as 2-3 degree of activity last exacerbation, with family history. Found a strong inverse correlation between the levels of DDR1 and IGF-1, and the line with TGF-β1 and β2-MG of blood and urine. In patients with obstructive HP DDR1 level was significantly higher than in patients with non-obstructive clinical form. Conclusions: Increased serum DDR1 shows the progression of kidney damage with active fibrogenesis and inflammation in certain categories of patients with CP in a state of clinical and laboratory remission.

scholarly journals Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenxuan Jiao ◽  
Man Bai ◽  
Hanwei Yin ◽  
Jiayi Liu ◽  
Jing Sun ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Thioredoxin Reductase ◽  
Transforming Growth Factor Β1 ◽  
Therapeutic Effects ◽  
Pathological State ◽  
Tgf Β1

Liver fibrosis is an important stage in the progression of liver injury into cirrhosis or even liver cancer. Hepatic stellate cells (HSCs) are induced by transforming growth factor-β1 (TGF-β1) to produce α-smooth muscle actin (α-SMA) and collagens in liver fibrosis. Butaselen (BS), which was previously synthesized by our group, is an organic selenium compound that exerts antioxidant and tumor cell apoptosis–promoting effects by inhibiting the thioredoxin (Trx)/thioredoxin reductase (TrxR) system. The aim of this study was to investigate the potential effects of BS on liver fibrosis and explore the underlying molecular mechanisms of its action. Liver fibrosis models were established using male BALB/c mice through intraperitoneal injection of CCl4. BS was administered orally once daily at a dose of 36, 90, or 180 mg/kg. Silymarin (Si), which is a drug used for patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, was administered at a dose of 30 mg/kg per day as a control. The action mechanisms of BS against liver fibrosis progression were examined in HSCs. The study revealed that the activity and expression levels of TrxR were elevated in the mouse liver and serum after CCl4-induced liver fibrosis. Oral administration of BS relieved the pathological state of mice with liver fibrosis, showing significant therapeutic effects against liver fibrosis. Moreover, BS not only induced HSC apoptosis but also inhibited the production of α-SMA and collagens by HSCs by downregulating the TGF-β1 expression and blocking the TGF-β1/Smads pathway. The results of the study indicated that BS inhibited liver fibrosis by regulating the TGF-β1/Smads pathway.

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