Paeoniflorin inhibits TGF-β1-mediated collagen production bySchistosoma japonicumsoluble egg antigenin vitro

Parasitology ◽  
2007 ◽  
Vol 134 (11) ◽  
pp. 1611-1621 ◽  
Author(s):  
D. CHU ◽  
Q. LUO ◽  
C. LI ◽  
Y. GAO ◽  
L. YU ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Peritoneal Macrophages ◽  
Type I ◽  
Smad3 Expression ◽  
Egg Antigen ◽  
Tgf Β1

SUMMARYThe main pathological characteristics of hepatic fibrosis in schistosomiasis are the proliferation of hepatic stellate cells (HSCs) and the deposition of collagen type I (Col I) and collagen type III (Col III). Transforming growth factor beta-1 (TGF-β1) plays an important role in hepatic fibrosis. Paeoniflorin (PAE) has been reported to have immunoregulatory effects; however, the mechanism of its anti-hepatic fibrosis inS. japonicumhas not been elucidated. In the present study, we found that mouse peritoneal macrophages (PMφs) stimulated by soluble egg antigen (SEA) ofS. japonicumcould secrete TGF-β1, and the TGF-β1 in the peritoneal macrophage-conditioned medium (PMCM) could induce proliferation of HSCs and secretion of Col I and III. We selected PMCM at 1:2 dilution as the optimum PMCM (OPMCM). Then we treated HSCs pre-incubated with OPMCM with PAE, and found that the inhibition of HSC proliferation or Col I and III production were closely correlated with the concentration of PAE. Further investigation found that PAE significantly decreased the Smad3 transcription and phosphorylation in HSCs stimulated by OPMCM. In conclusion, SEA plays a key role in hepatic fibrosis by inducing TGF-β1 from PMφs. PAE can exert anti-fibrogenic effects by inhibiting HSCs proliferation and down-regulating Smad3 expression and phosphorylation through TGF-β1 signalling.

Stretching-Induced Collagen Type I Synthesis in Human Tendon Fibroblasts Is Mediated by TGF-β1

2003 ◽  
Author(s):  
Guoguang Yang ◽  
Richard C. Crawford ◽  
James H.-C. Wang
Keyword(s):  
Protein Synthesis ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Type I ◽  
Dependent Manner ◽  
Gene And Protein Expression ◽  
Mechanical Stretching ◽  
Tgf Β1

This study investigated the effect of cyclic mechanical stretching on the collagen gene expression and protein synthesis of human patellar tendon fibroblasts (HPTFs). We hypothesized that cyclic mechanical stretching of HPTFs would increase collagen synthesis via transforming growth factor-beta 1 (TGF-β1). To test the hypothesis, the tendon fibroblasts were cultured on microgrooved surfaces of silicone dishes under serum-free conditions. The cells were subjected to cyclic uniaxial stretching with a constant frequency and duration (0.5Hz, 4hr), and one of three stretching magnitudes (no stretch, 4%, and 8%) followed by 4 hours of rest. It was found that the gene and protein expression of both collagen type I and TGF-β1 were significantly increased in a stretching-magnitude dependent manner, whereas collagen type III gene and protein levels were not significantly changed. The exogenous addition of antibody to TGF-β1 eliminated the stretching-induced increase in collagen type I protein synthesis. The results therefore confirmed our working hypothesis and suggest that mechanical stretching of tendon fibroblasts can lead to matrix remodeling by modulating the collagen production of tendon fibroblasts, a process at least particially mediated by TGF-β1.

scholarly journals Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

2016 ◽  
Vol 10 (5-6) ◽  
pp. 175 ◽  
Author(s):  
Premsant Sangkum ◽  
Faysal A. Yafi ◽  
Hogyoung Kim ◽  
Mostafa Bouljihad ◽  
Manish Ranjan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Rat Model ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Type I ◽  
Sprague Dawley ◽  
Group 10 ◽  
Tgf Β1

Introduction: We sought to evaluate the therapeutic effect of adipose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis.Methods: Eighteen (18) male Sprague-Dawley rats (300‒350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 μg transforming growth factor beta 1 (TGF-β1) injection); and (3) ADSCs group (10 μg TGF-β1 injection plus 2 x 105 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks afterurethral injection. Following euthanasia, rat urethral tissue was were quantitated by Western blot analysis. Results: TGF-β1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-β1 induced fibrotic changes were ameliorated by injection of ADSCs.Conclusions: Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results.

scholarly journals Calvaria Bone Transcriptome in Mouse Models of Osteogenesis Imperfecta

2021 ◽  
Vol 22 (10) ◽  
pp. 5290
Author(s):  
Pierre Moffatt ◽  
Iris Boraschi-Diaz ◽  
Juliana Marulanda ◽  
Ghalib Bardai ◽  
Frank Rauch
Keyword(s):  
Osteogenesis Imperfecta ◽  
Mouse Models ◽  
Transforming Growth Factor Beta ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Type I ◽  
Growth Factor Beta ◽  
Upregulated Genes

Osteogenesis imperfecta (OI) is a bone fragility disorder that is usually caused by mutations affecting collagen type I. We compared the calvaria bone tissue transcriptome of male 10-week-old heterozygous Jrt (Col1a1 mutation) and homozygous oim mice (Col1a2 mutation) to their respective littermate results. We found that Jrt and oim mice shared 185 differentially expressed genes (upregulated: 106 genes; downregulated: 79 genes). A total of seven genes were upregulated by a factor of two or more in both mouse models (Cyp2e1, Slc13a5, Cgref1, Smpd3, Ifitm5, Cthrc1 and Rerg). One gene (Gypa, coding for a blood group antigen) was downregulated by a factor of two or more in both OI mouse models. Overrepresentation analyses revealed that genes involved in ‘ossification’ were significantly overrepresented among upregulated genes in both Jrt and oim mice, whereas hematopoietic genes were downregulated. Several genes involved in Wnt signaling and transforming growth factor beta signaling were upregulated in oim mice, but less so in Jrt mice. Thus, this study identified a set of genes that are dysregulated across various OI mouse models and are likely to play an important role in the pathophysiology of this disorder.

scholarly journals High Glucose Stimulates Proliferation and Collagen Type I Synthesis in Renal Cortical Fibroblasts

1999 ◽  
Vol 10 (9) ◽  
pp. 1891-1899 ◽  
Author(s):  
DONG CHEOL HAN ◽  
MOTOHIDE ISONO ◽  
BRENDA B. HOFFMAN ◽  
FUAD N. ZIYADEH
Keyword(s):  
High Glucose ◽  
Type I Collagen ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Thymidine Incorporation ◽  
Collagen Type I ◽  
Type I ◽  
Dependent Manner ◽  
Collagen Mrna ◽  
Tgf Β1

Abstract. Renal tubular epithelial cells and interstitial fibroblasts are active participants in tubulointerstitial fibrosis, the best correlate of decreased glomerular filtration in diabetic nephropathy. It was reported previously that high ambient glucose stimulates transforming growth factor-β (TGF-β) mRNA and bioactivity, promotes cellular hypertrophy, and increases collagen synthesis in proximal tubular cells. This study evaluates the effects of high glucose and TGF-β on the behavior of murine renal cortical fibroblasts (TFB) in culture. High glucose (450 mg/dl) significantly increased [3H]-thymidine incorporation (by 60 to 80% after 24 to 72 h) and cell number, without significantly increasing cell death when compared with normal glucose (100 mg/dl). There also was a transient increase in the mRNA of the c-mycandegr-1early-response genes. Exogenous TGF-β1 was promitogenic rather than antiproliferative in contrast to other renal cell types. Northern blot analysis demonstrated constitutive expression of TGF-β1, -β2, and -β3 transcripts. Exposure to high glucose increased all three TGF-β isoforms in a time-dependent manner. High glucose as well as exogenous TGF-β1 also increased [3H]-proline incorporation, α2(I) collagen mRNA, and type I collagen protein (measured by immunoassay). Treatment with a neutralizing pan-selective monoclonal anti-TGF-β antibody markedly attenuated the stimulation by high ambient glucose of thymidine incorporation, TGF-β1 mRNA, and type I collagen mRNA and protein levels. It is concluded that high ambient glucose and exogenous TGF-β1 share similar actions on renal fibroblasts. Moreover, the stimulation of cell proliferation and collagen type I synthesis in these cells by high ambient glucose are mediated by activation of an autocrine TGF-β system.

scholarly journals Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells through the Inhibition of the TGF-β1-Induced SMAD2/3 Signaling Pathway

2019 ◽  
Vol 20 (24) ◽  
pp. 6314 ◽  
Author(s):  
Mattareeyapar Phaosri ◽  
Salinee Jantrapirom ◽  
Mingkwan Na Takuathung ◽  
Noppamas Soonthornchareonnon ◽  
Seewaboon Sireeratawong ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Collagen Type ◽  
Stellate Cell ◽  
Scientific Evidence ◽  
Collagen Type I ◽  
Type I ◽  
Noticeable Increase ◽  
Stem Extract ◽  
Collagen Type 1 ◽  
Tgf Β1

Salacia chinensis L. (SC) stems have been used as an ingredient in Thai traditional medicine for treating patients with hepatic fibrosis and liver cirrhosis. However, there is no scientific evidence supporting the antifibrotic effects of SC extract. Therefore, this study aimed to determine the antifibrotic activity of SC stem extract in human hepatic stellate cell-line called LX-2. We found that upon TGF-β1 stimulation, LX-2 cells transformed to a myofibroblast-like phenotype with a noticeable increase in α-SMA and collagen type I production. Interestingly, cells treated with SC extract significantly suppressed α-SMA and collagen type I production and reversed the myofibroblast-like characteristics back to normal. Additionally, TGF-β1 also influenced the development of fibrogenesis by upregulation of MMP-2, TIMP-1, and TIMP-2 and related cellular signaling, such as pSmad2/3, pErk1/2, and pJNK. Surprisingly, SC possesses antifibrotic activity through the suppression of TGF-β1-mediated production of collagen type 1, α-SMA, and the phosphorylation status of Smad2/3, Erk1/2, and JNK. Taken together, the present study provides accumulated information demonstrating the antifibrotic effects of SC stem extract and revealing its potential for development for hepatic fibrosis patients.

scholarly journals The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis

2021 ◽  
Author(s):  
Hak Su Kim ◽  
Su-Jin Moon ◽  
Sang Eun Lee ◽  
Gi Won Hwang ◽  
Hyun Ju Yoo ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Pulmonary Fibrosis ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Arachidonic Acid Metabolite ◽  
Type I ◽  
Induced Expression ◽  
Primary Fibroblasts ◽  
Tgf Β1

AbstractEpoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that are rapidly metabolized into diols by soluble epoxide hydrolase (sEH). sEH inhibition has been shown to increase the biological activity of EETs, which are known to have anti-inflammatory properties. However, the role of EETs in pulmonary fibrosis remains unexplored. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze EETs in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF, n = 29) and controls (n = 15), and the function of 11,12-EET was evaluated in in vitro and in vivo in pulmonary fibrosis models. EET levels in IPF lung tissues, including those of 8,9-EET, 11,12-EET, and 14,15-EET, were significantly lower than those in control tissues. The 11,12-EET/11,12-DHET ratio in human lung tissues also differentiated IPF from control tissues. 11,12-EET significantly decreased transforming growth factor (TGF)-β1-induced expression of α-smooth muscle actin (SMA) and collagen type-I in MRC-5 cells and primary fibroblasts from IPF patients. sEH-specific siRNA and 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU; sEH inhibitor) also decreased TGF-β1-induced expression of α-SMA and collagen type-I in fibroblasts. Moreover, 11,12-EET and TPPU decreased TGF-β1-induced p-Smad2/3 and extracellular-signal-regulated kinase (ERK) expression in primary fibroblasts from patients with IPF and fibronectin expression in Beas-2B cells. TPPU decreased the levels of hydroxyproline in the lungs of bleomycin-induced mice. 11,12-EET or sEH inhibitors could inhibit pulmonary fibrosis by regulating TGF-β1-induced profibrotic signaling, suggesting that 11,12-EET and the regulation of EETs could serve as potential therapeutic targets for IPF treatment.

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