scholarly journals Cadmium inhibits placental trophoblast cell migration via miRNA regulation of the transforming growth factor beta (TGF-β) pathway

2017 ◽  
Vol 109 ◽  
pp. 721-726 ◽  
Author(s):  
Samira A. Brooks ◽  
Rebecca C. Fry
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Trophoblast Cell ◽  
Mirna Regulation ◽  
Growth Factor Beta

scholarly journals Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration.

1991 ◽  
Vol 113 (6) ◽  
pp. 1439-1445 ◽  
Author(s):  
S Kojima ◽  
P C Harpel ◽  
D B Rifkin
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Culture Medium ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Smooth Muscle Cell Migration ◽  
Growth Factor Beta

Conditioned medium (CM) derived from co-cultures of bovine aortic endothelial cells (BAECs) and bovine smooth muscle cells (BSMCs) contains transforming growth factor-beta (TGF-beta) formed via a plasmin-dependent activation of latent TGF-beta (LTGF beta), which occurs in heterotypic but not in homotypic cultures (Sato, Y., and D. B. Rifkin. 1989. J. Cell Biol. 107: 1199-1205). The TGF-beta formed is able to block the migration of BSMCs or BAECs. We have found that the simultaneous addition to heterotypic culture medium of plasminogen and the atherogenic lipoprotein, lipoprotein (a) (Lp(a)), which contains plasminogen-like kringles, inhibits the activation of LTGF-beta in a dose-dependent manner. The inclusion of LDL in the culture medium did not show such an effect. Control experiments indicated that Lp(a) does not interfere with the basal level of cell migration, the activity of exogenous added TGF-beta, the release of LTGF-beta from cells, the activation of LTGF-beta either by plasmin or by transient acidification, or the activity of plasminogen activator. The addition of Lp(a) to the culture medium decreased the amount of plasmin found in BAECs/BSMCs cultures. Similar results were obtained using CM derived from cocultures of human umbilical vein endothelial cells and human foreskin fibroblasts. These results suggest that Lp(a) can inhibit the activation of LTGF-beta by competing with the binding of plasminogen to cell or matrix surfaces. Therefore, high plasma levels of Lp(a) might enhance smooth muscle cell migration by decreasing the levels of the migration inhibitor TGF-beta thus contributing to generation of the atheromatous lesions.

GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression

Reproduction ◽  
2021 ◽  
Author(s):  
Lanlan Fang ◽  
Zhen Wang ◽  
Ze Wu ◽  
Yang Yan ◽  
Yibo Gao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Invasion ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Trophoblast Cell ◽  
Human Trophoblast ◽  
Growth Factor Beta ◽  
Cell Invasiveness ◽  
Extravillous Cytotrophoblast ◽  
Placental Diseases

Matrix metalloproteinases (MMPs) play a pivotal role in the regulation of cell invasion. Placental trophoblast cell invasion is a precisely regulated event. Dysregulation of MMPs has been linked to various placental diseases. Growth differentiation factor-8 (GDF-8), also known as myostatin, is a member of the transforming growth factor-beta (TGF-β) superfamily. GDF-8 and its putative receptors are expressed in human extravillous cytotrophoblast cells (EVTs). Although the pro-invasive effect of GDF-8 in human EVT cells has been recently reported, the underlying molecular mechanism remains largely unknown. In this study, we investigate the effects of GDF-8 on the expression of the two most important MMPs, MMP2 and MMP9, in the HTR-8/SVneo human EVT cell line. Our results show that GDF-8 significantly upregulates the expression of MMP2. The expression of MMP9 is not affected by GDF-8. Using a siRNA-mediated knockdown approach, we reveal that the stimulatory effect of GDF-8 on MMP2 expression is mediated by the ALK5-SMAD2/3 signaling pathway. Additionally, the knockdown of MMP2 attenuates the GDF-8-induced cell invasiveness. These findings deepen our understanding of the biological roles of GDF-8 in the regulation of human trophoblast cell invasion.

Polyamines are necessary for normal expression of the transforming growth factor-beta gene during cell migration

1997 ◽  
Vol 272 (4) ◽  
pp. G713-G720 ◽  
Author(s):  
J. Y. Wang ◽  
M. J. Viar ◽  
J. Li ◽  
H. J. Shi ◽  
S. A. McCormack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Epithelial Cell Migration ◽  
Growth Factor Beta ◽  
Beta Gene

The current study tests the hypothesis that intracellular polyamines are involved in the regulation of gene expression of transforming growth factor-beta (TGF-beta) during epithelial cell migration after wounding. Administration of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (the first rate-limiting enzyme for polyamine synthesis), depleted cellular polyamines putrescine, spermidine, and spermine in IEC-6 cells. DFMO also significantly reduced basal levels of TGF-beta mRNA in unwounded cells. Gene expression of TGF-beta was dramatically stimulated after wounding of a monolayer of cells not treated with DFMO. TGF-beta mRNA levels significantly increased from 4 to 12 h after wounding, peaking at 6 h at a level eight times the prewounding control. Increased levels of TGF-beta mRNA in IEC-6 cells after wounding were paralleled by an increase in TGF-beta content. Depletion of intracellular polyamines in DFMO-treated cells significantly inhibited increased expression of the TGF-beta gene in response to wounding. Cell migration also significantly decreased in DFMO-treated cells. In the presence of DFMO, exogenous TGF-beta restored cell migration to normal. These results indicate that 1) polyamine depletion induced by DFMO is associated with decreases in the expression of the TGF-beta gene and cell migration in IEC-6 cells and 2) exogenous TGF-beta reverses the inhibitory effect of polyamine depletion on cell migration. These findings suggest that polyamines are required for epithelial cell migration in association with their ability to regulate TGF-beta gene expression.

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