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.

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.

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 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.

Repetitive mechanical stretching modulates transforming growth factor-β induced collagen synthesis and apoptosis in human patellar tendon fibroblasts

2012 ◽  
Vol 90 (5) ◽  
pp. 667-674 ◽  
Author(s):  
Chaoyin Jiang ◽  
Lei Shao ◽  
Qiaojie Wang ◽  
Yang Dong
Keyword(s):  
Growth Factor ◽  
Patellar Tendon ◽  
Collagen Synthesis ◽  
Molecular Mechanisms ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Parp Cleavage ◽  
Type I ◽  
Mechanical Stretching

The cellular and molecular mechanisms underlying the development of tendinopathy are not clear, but inflammatory mediators produced by tendon fibroblasts in response to repetitive mechanical loading may be an important factor for this illness. In this study, we explored the effect of cyclic mechanical stretching on collagen synthesis and apoptosis of human patellar tendon fibroblasts (HPTFs). The role of a candidate inflammatory mediator, transforming growth factor-β1 (TGFβ1), which we identified in a cytokine antibody array, in collagen synthesis and apoptosis during repetitive mechanical stretching was also investigated. Our results showed that there was a significant increase in collagen type I synthesis at 4% and 8% stretch. Significantly, enhancement of apoptosis may account for the observed decrease in fibroblast numbers after 8% stretching. Furthermore, the exogenous addition of an anti-TGFβ1 antibody or gene silencing by si-TGFβ1 eliminated the increase in collagen type I production and activities of caspases during apoptosis under cyclic uniaxial stretching conditions. These results suggest that TGFβ1 may take part in the increase of cellular production of collagen type I and apoptosis during the development of tendinopathy. Furthermore, caspase 8 mediates activation of caspase 3 and poly ADP-ribose polymerase (PARP) cleavage during TGFβ1-induced apoptosis in stretching HPTFs.

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