scholarly journals Tiaoshen Tongluo Attenuates Fibrosis by Modulating the TGF-β1/Smad Pathway in Endometrial Stromal Cells and a Rat Model of Intrauterine Adhesion

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hongping Niu ◽  
Xiaoling Miao ◽  
Xingxiu Zhan ◽  
Xiaona Zhou ◽  
Xingyan Li ◽  
...  
Keyword(s):  
Rat Model ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Endometrial Stromal Cells ◽  
Smad Pathway ◽  
Intrauterine Adhesion ◽  
Smad4 Expression ◽  
Tgf Β1

Intrauterine adhesion (IUA) is a serious complication caused by excessive fibrosis resulting from endometrial repair after trauma. The traditional Chinese medicine Tiaoshen Tongluo recipe (TTR) contains ingredients associated with the alleviation of fibrosis. The transforming growth factor-β1 (TGF-β1)/Smad pathway is thought to mediate fibrosis in IUA. In this study, we evaluated the influence of TTR on endometrial fibrosis in a rat model of IUA and in TGF-β1-stimulated endometrial stromal cells (ESCs). TTR was found to alleviate the level of endometrial fibrosis in a rat model of IUA. A higher number of collagen fibers and greater damage were observed in the endometrial tissue of untreated rats compared to those treated with TTR. The expression of TGF-β1, Smad2, Smad3, and Smad4 was upregulated following IUA, whereas Smad7 expression was downregulated. TTR lowers the expression of TGF-β1, Smad2, Smad3, and Smad4 but increases the expression of Smad7 in vivo, indicating that TTR can modulate the expression of the TGF-β1/Smad pathway to mediate fibrosis. In ESCs, the phosphorylation of Smad2 and Smad3 and upregulation of Smad4 were induced by TGF-β1 whereas the expression of Smad7 was inhibited. Administration of TTR reduces the phosphorylation of Smad2 and Smad3, increases Smad4 expression induced by TGF-β1, and promotes the expression of Smad7. TTR modulates the TGF-β1/Smad pathway to alleviate the generation of fibrotic tissue in response to IUA.

scholarly journals microRNA-145-5p attenuates acute lung injury via targeting ETS2

2021 ◽  
Author(s):  
Liang Qiao ◽  
Rongxia Li ◽  
Shangang Hu ◽  
Yu Liu ◽  
Hongqiang Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Growth Factor ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Recombinant Adenovirus ◽  
Transforming Growth Factor Β1 ◽  
Inflammatory Factors ◽  
Smad Pathway ◽  
Tgf Β1

Abstract Objective Previously, the protective effect of microRNA (miR)-145-5p has been discovered in acute lung injury (ALI). Thus, this study attempts to further discuss the mechanism of miR-145-5p in ALI through the downstream E26 transformation-specific proto-oncogene 2 (ETS2)/transforming growth factor β1 (TGF-β1)/Smad pathway. Methods A lipopolysaccharide (LPS)-induced rat ALI model was established. Recombinant adenovirus miR-145-5p and/or ETS2 overexpression plasmid was administrated into rats. Afterwards, pathological damage in the lung tissue, wet/dry (W/D) ratio, apoptosis and contents of serum inflammatory factors were observed. miR-145-5p, ETS2, TGF-β1, Smad2/3, phosphorylated Smad2/3 levels were measured in rats. Results miR-145-5p was down-regulated, ETS2 was up-regulated and TGF-β1/Smad pathway was activated in LPS-suffered rats. Overexpression of miR-145-5p inactivated the TGF-β1/Smad pathway and attenuated ALI, as reflected by relived pathological damage, and decreased W/D ratio, apoptosis and inflammatory response. Oppositely, loss of miR-145-5p or enhancement of ETS2 worsened ALI and activated the TGF-β1/Smad pathway. Moreover, elevation of ETS2 decreased miR-145-5p-mediated protection against ALI. Conclusion Evidently, miR-145-5p negatively regulates ETS2 expression and inactivates TGF-β1/Smad pathway to ameliorate ALI in rats.

scholarly journals Dual Regulation of Proliferation and Growth Arrest in Prostatic Stromal Cells by Transforming Growth Factor-β1

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4280-4284 ◽  
Author(s):  
Wei Zhou ◽  
Irwin Park ◽  
Michael Pins ◽  
James M. Kozlowski ◽  
Borko Jovanovic ◽  
...  
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Culture Medium ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Growth Arrest ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β1 ◽  
Dual Effect ◽  
Tgf Β1

In a preliminary study, we observed that TGF-β1 induced both proliferation and growth arrest in prostatic stromal cells, depending on the concentration of TGF-β1 used in the culture medium. In this study, we explored possible mechanisms of this dual effect of TGF-β. Primary cultures of prostatic stromal cells, established from clinical surgical specimens and treated with low doses of TGF-β1 (0.001–0.01 ng/ml), resulted in an increase in cell proliferation. The addition of neutralizing antibody against platelet-derived growth factor (PDGF)-BB, but not anti-PDGF-AA, abrogated this stimulatory effect of TGF-β1. TGF-β1 treatment resulted in a dose-related increase in PDGF-BB production as measured by ELISA. Cells underwent growth arrest at high concentrations of TGF-β1 (1.0 and 10 ng/ml). An inhibitor of cyclin-dependent kinase (cdk), p15INK4b, was up-regulated at both transcript and protein levels in these cultures by TGF-β1 in a dose-related manner as determined by RT-PCR and Western blot analysis. The transcript, but not the protein, for another cdk inhibitor, p21Cip1, was up-regulated with treatment of TGF-β1 to these cells. Levels of other cdk inhibitors, such as p16INK4a and p27Kip1, were constitutively expressed in prostatic stromal cells and were not significantly affected by TGF-β1 treatment. Finally, the growth arrest effect of TGF-β1 was abrogated when antisense oligonucleotides to p15INH4b, but not p21Cip1, were added to the culture medium. These data indicate that the dual effect of TGF-β1 is mediated, at least, by up-regulation of PDGF-BB and p15INK4b, respectively.

Identification of Platelet Releasate Proteins that Bind to Mastoparan, a Peptide that Inhibits Shear-Induced TGF-β1 Activation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3271-3271
Author(s):  
Teresa M Brophy ◽  
Jasimuddin Ahamed ◽  
Barry S. Coller
Keyword(s):  
Transforming Growth Factor ◽  
Coagulation Factor ◽  
Transforming Growth Factor Β1 ◽  
Affinity Column ◽  
Factor V ◽  
Disulfide Exchange ◽  
Control Peptide ◽  
Tgf Β1

Abstract Abstract 3271 Transforming growth factor β1 (TGF-β1) is a disulfide-bonded, 25 kD homodimeric protein produced by most cell types, including platelets, that functions as a cytokine in many physiologic and pathologic processes. Platelets contain 40–100 times more TGF-β1 than other cells and release it as an inactive large latent complex (LLC) comprised of TGF-β1 non-covalently associated with its latency-associated peptide (LAP), which is, in turn, disulfide-bonded to latent TGF-β binding protein 1 (LTBP-1). Thrombospondin-1 (TSP1), proteases, and reactive oxygen species have all been shown to activate TGF-β1 in vitro and a role for integrins in vivo has been inferred from studies of transgenic mice. Recently, we discovered that shear force can activate latent TGF-β1 released from platelets in vitro and that thiol-disulfide exchange contributes to shear-dependent TGF-β1 activation. A number of thiol isomerase enzymes that can catalyze thiol-disulfide exchange have been identified in platelets, including protein disulfide isomerase (PDI), ERp5, ERp57, ERp72, ERp44, ERp29, and TMX3. As shear-induced activation of TGF-β1 is partially thiol-dependent, we investigated if thiol isomerases can affect this process. Mastoparan is a non-thiol-containing wasp venom peptide known to inhibit the chaperone activity of PDI, ERp5, and perhaps other thiol isomerases. We recently showed that mastoparan, (INLKALAALAKKIL), inhibits stirring-induced TGF-β1 activation by more than 90% (100 μM; n=3, p=0.03), whereas no inhibition was observed with an inactive mastoparan-like control peptide (INLKAKAALAKKLL) at 100 μM (n=3, p=0.66). To identify the proteins that bind to mastoparan, either directly or indirectly, platelet releasates were chromatographed on a mastoparan affinity column prepared from N-hydroxysuccinimide Sepharose. Two control columns were employed: 1. unconjugated Sepharose, and 2. Sepharose conjugated with the mastoparan-like control peptide. Elution of bound proteins was achieved by increasing the NaCl concentration. Proteins identified by mass spectrometry as specifically binding to the mastoparan peptide column included LTBP-1, TGF-β1 precursor, clusterin, coagulation Factor V, multimerin-1, 14-3-3 protein zeta/delta, and α-actinin 4. These results were confirmed by immunoblotting. Furthermore, the thiol isomerases PDI, ERp5, ERp57, and ERp72 were all found to bind specifically to mastoparan as confirmed by immunoblotting. We conclude that mastoparan affinity chromatography identified a number of proteins in platelet releasates that may contribute to shear-induced TGF-β1 activation. Disclosures: Coller: Centocor/Accumetrics/Rockefeller University:.

CD28 disruption exacerbates inflammation in Tgf-β1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-β1

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4594-4601 ◽  
Author(s):  
Mizuko Mamura ◽  
WoonKyu Lee ◽  
Timothy J. Sullivan ◽  
Angelina Felici ◽  
Anastasia L. Sowers ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Necrosis Factor Receptor ◽  
Transforming Growth Factor Β1 ◽  
Autoimmune Inflammatory Disease ◽  
Lymph Node Cells ◽  
Tgf Β1

Abstract Tgf-β1-/- mice develop a progressive, lethal, inflammatory syndrome, but mechanisms leading to the spontaneous activation of Tgf-β1-/- T cells remain unclear. Here we show the disruption of CD28 gene expression accelerates disease in Tgf-β1-/- mice, and we link this increase in severity to a reduction in the number of CD4+CD25+ regulatory T cells. CD4+CD25+ T cells develop normally in Tgf-β1-/- mice and display characteristic expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), αEβ7 integrin, and Foxp3. Adoptive transfer of Tgf-β1-/- splenocytes to Tgf-β1+/+/Rag2-/- mice induced an autoimmune inflammatory disease with features similar to those of the Tgf-β1-/- phenotype, and disease transfer was accelerated by the depletion of Tgf-β1-/- CD4+CD25+ T cells from donor splenocytes. Cotransfer of Tgf- β1-/- CD4+CD25+ T cells clearly attenuated disease in Rag2-/- recipients of CD25+-depleted Tgf-β1-/- spleen and lymph node cells, but suppression was incomplete when compared with Tgf-β1+/+ CD4+CD25+ T cells. These data demonstrate that CD4+CD25+ regulatory T cells develop in complete absence of endogenous transforming growth factor-β1 (TGF-β1) expression and that autocrine TGF-β1 expression is not essential for these cells to suppress inflammation in vivo. (Blood. 2004;103:4594-4601)

Comparison of Release Profiles of Various Growth Factors from Biodegradable Carriers

1998 ◽  
Vol 530 ◽  
Author(s):  
Y. Tabata ◽  
M. Yamamoto ◽  
Y. Ikada
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
The Body ◽  
Bone Morphogenetic Protein 2 ◽  
Biodegradable Hydrogel ◽  
Tgf Β1

AbstractA biodegradable hydrogel was prepared by glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 as a carrier to release basic growth factors on the basis of polyion complexation. Basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) were sorbed from their aqueous solution into the dried gelatin hydrogels to prepare respective growth factor-incorporating hydrogels. Under an in vitro non-degradation condition, approximately 20 % of incorporated bFGF and TGF-β1 was released from the hydrogels within initial 40 min, followed by no further release, whereas a large initial release of BMP-2 was observed. After subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled growth factor in the mouse back, the remaining radioactivity was measured to estimate the in vivo release profile of growth factors. Incorporation into gelatin hydrogels enabled bFGF and TGF-β1 to retain in the body for about 15 days and the retention period well correlated with that of the gelatin hydrogel. Taken together, it is likely that the growth factors ionically complexed with acidic gelatin were released in vivo as a result of hydrogel biodegradation. On the contrary, basic BMP-2 did not ionically interact with acidic gelatin, resulting in no sustained released by the present biodegradable carrier system.

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