scholarly journals Bistable switch in migration stimulating factor expression: Regulation by the concerted signalling of transforming growth factor-β1 and the extracellular matrix

2011 ◽  
Vol 130 (9) ◽  
pp. 2024-2032 ◽  
Author(s):  
Seth L. Schor ◽  
Ian R. Ellis ◽  
Sarah J. Jones ◽  
Anne-Marie Woolston ◽  
Ana M. Schor
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Expression Regulation ◽  
Bistable Switch ◽  
Factor Expression ◽  
Migration Stimulating Factor ◽  
Stimulating Factor

Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

2021 ◽  
Vol 19 (4) ◽  
pp. 501-507
Author(s):  
Yunhe Gu ◽  
Peiyao Guo ◽  
Guangbiao Xu
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Extracellular Matrix Deposition ◽  
Dose Dependent

Transforming growth factor-β1 promotes excessive extracellular matrix deposition and epithelial-mesenchymal transition of tubular epithelial cells, thus stimulating the progression of renal fibrosis. Carvacrol has been shown to alleviate cardiac and liver fibrosis and attenuate renal injury. However, the role of carvacrol on renal fibrosis has not been examined. First, measurements using Cell Counting Kit-8 showed that carvacrol reduced cell viability of tubular epithelial cell line HK-2 in a dose-dependent fashion. Second, transforming growth factor-β1 induced excessive extracellular matrix deposition in HK-2 cells with enhanced collagen I, collagen IV, and fibronectin expression. However, carvacrol decreased the expression of collagen I, collagen IV in a dose-dependent manner and fibronectin to attenuate the extracellular matrix deposition in HK-2. Third, carvacrol attenuated TGF-β1-induced decrease of E-cadherin and increase of snail, vimentin, and alpha-smooth muscle actin in HK-2 cells. Transforming growth factor-β1-induced increase in PI3K and AKT phosphorylation in HK-2 were also reversed by carvacrol. Collectively, carvacrol ameliorates renal fibrosis through inhibition of transforming growth factor-β1-induced extracellular matrix deposition and epithelial-mesenchymal transition of HK-2 cells, providing potential therapy for the treatment of renal fibrosis.

scholarly journals The Signaling Network of Transforming Growth Factor β1, Protein Kinase Cδ, and Integrin Underlies the Spreading and Invasiveness of Gastric Carcinoma Cells

2005 ◽  
Vol 25 (16) ◽  
pp. 6921-6936 ◽  
Author(s):  
Mi-Sook Lee ◽  
Tae Young Kim ◽  
Yong-Bae Kim ◽  
Sung-Yul Lee ◽  
Seong-Gyu Ko ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Gastric Carcinoma ◽  
Transforming Growth Factor ◽  
Carcinoma Cell ◽  
Cell Spreading ◽  
Transforming Growth Factor Β1 ◽  
Gastric Carcinoma Cell ◽  
Spreading Behavior ◽  
Protein Kinase Cδ

ABSTRACT Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor β1 (TGFβ1) pathway that is mediated by protein kinase Cδ (PKCδ). TGFβ1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCδ, which is required for expression and activation of integrins. Increased expression of integrins α2 and α3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFβ1 effects. Furthermore, TGFβ1 treatment and PKCδ activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGFβ pathway, PKCδ expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.

scholarly journals Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix

2007 ◽  
Vol 179 (6) ◽  
pp. 1311-1323 ◽  
Author(s):  
Pierre-Jean Wipff ◽  
Daniel B. Rifkin ◽  
Jean-Jacques Meister ◽  
Boris Hinz
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Mechanical Stress ◽  
Protease Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Stress Fibers ◽  
Fibrotic Diseases ◽  
Triton X ◽  
Tgf Β1

The conjunctive presence of mechanical stress and active transforming growth factor β1 (TGF-β1) is essential to convert fibroblasts into contractile myofibroblasts, which cause tissue contractures in fibrotic diseases. Using cultured myofibroblasts and conditions that permit tension modulation on the extracellular matrix (ECM), we establish that myofibroblast contraction functions as a mechanism to directly activate TGF-β1 from self-generated stores in the ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with Triton X-100 releases active TGF-β1 from the ECM. This process is inhibited either by antagonizing integrins or reducing ECM compliance and is independent from protease activity. Stretching myofibroblast-derived ECM in the presence of mechanically apposing stress fibers immediately activates latent TGF-β1. In myofibroblast-populated wounds, activation of the downstream targets of TGF-β1 signaling Smad2/3 is higher in stressed compared to relaxed tissues despite similar levels of total TGF-β1 and its receptor. We propose activation of TGF-β1 via integrin-mediated myofibroblast contraction as a potential checkpoint in the progression of fibrosis, restricting autocrine generation of myofibroblasts to a stiffened ECM.

Sign in / Sign up

Export Citation Format

Share Document