scholarly journals Insulin-Like Growth Factor-I Enhances Transforming Growth Factor-β-Induced Extracellular Matrix Protein Production Through the P38/Activating Transcription Factor-2 Signaling Pathway in Keloid Fibroblasts

2003 ◽  
Vol 120 (6) ◽  
pp. 956-962 ◽  
Author(s):  
Takehiro Daian ◽  
Hiroshi Ishihara ◽  
Akiyoshi Hirano ◽  
Tohru Fujii ◽  
Akira Ohtsuru ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Protein Production ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Extracellular Matrix Protein ◽  
Factor I ◽  
Activating Transcription Factor ◽  
Keloid Fibroblasts

scholarly journals Identification of the growth factor–binding sequence in the extracellular matrix protein MAGP-1

2020 ◽  
Vol 295 (9) ◽  
pp. 2687-2697 ◽  
Author(s):  
Thomas J. Broekelmann ◽  
Nicholas K. Bodmer ◽  
Robert P. Mecham
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Extracellular Matrix Protein ◽  
Surface Plasmon Resonance Analysis ◽  
Factor Binding

Microfibril-associated glycoprotein-1 (MAGP-1) is a component of vertebrate extracellular matrix (ECM) microfibrils that, together with the fibrillins, contributes to microfibril function. Many of the phenotypes associated with MAGP-1 gene inactivation are consistent with dysregulation of the transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling system. We have previously shown that full-length MAGP-1 binds active TGFβ-1 and some BMPs. The work presented here further defines the growth factor–binding domain of MAGP-1. Using recombinant domains and synthetic peptides, along with surface plasmon resonance analysis to measure the kinetics of the MAGP-1–TGFβ-1 interaction, we localized the TGFβ- and BMP-binding site in MAGP-1 to a 19-amino acid–long, highly acidic sequence near the N terminus. This domain was specific for binding active, but not latent, TGFβ-1. Growth factor activity experiments revealed that TGFβ-1 retains signaling activity when complexed with MAGP-1. Furthermore, when bound to fibrillin, MAGP-1 retained the ability to interact with TGFβ-1, and active TGFβ-1 did not bind fibrillin in the absence of MAGP-1. The absence of MAGP was sufficient to raise the amount of total TGFβ stored in the ECM of cultured cells, suggesting that the MAGPs compete with the TGFβ large latent complex for binding to microfibrils. Together, these results indicate that MAGP-1 plays an active role in TGFβ signaling in the ECM.

scholarly journals Fibromodulin Modulates Chicken Skeletal Muscle Development via the Transforming Growth Factor-β Signaling Pathway

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1477
Author(s):  
Huadong Yin ◽  
Can Cui ◽  
Shunshun Han ◽  
Yuqi Chen ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Matrix Protein ◽  
Muscle Development ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Extracellular Matrix Protein ◽  
Skeletal Muscle Development

Fibromodulin (Fmod), which is an extracellular matrix protein, belongs to the extracellular matrix small-leucine-rich proteoglycan family. Fmod is abundantly expressed in muscles and connective tissues and is involved in biological regulation processes, including cell apoptosis, cell adhesion, and modulation of cytokine activity. Fmod is the main regulator of myostatin, which controls the development of muscle cells, but its regulatory path is unknown. Chicken models are ideal for studying embryonic skeletal muscle development; therefore, to investigate the mechanism of Fmod in muscle development, Fmod-silenced and Fmod-overexpressed chicken myoblasts were constructed. The results showed that Fmod plays a positive role in differentiation by detecting the expression of myogenic differentiation markers, immunofluorescence of MyHC protein, and myotube formation in myoblasts. Fmod regulates expression of atrophy-related genes to alleviate muscle atrophy, which was confirmed by histological analysis of breast muscles in Fmod-modulated chicks in vivo. Additionally, genes differentially expressed between Fmod knockdown and normal myoblasts were enriched in the signaling pathway of transforming growth factor β (TGF-β). Both Fmod-silenced and Fmod-overexpressed myoblasts regulated the expression of TGFBR1 and p-Smad3. Thus, Fmod can promote differentiation but not proliferation of myoblasts by regulating the TGF-β signaling pathway, which may serve a function in muscular atrophy.

Inhibiting albumin glycation attenuates dysregulation of VEGFR-1 and collagen IV subchain production and the development of renal insufficiency

2007 ◽  
Vol 292 (2) ◽  
pp. F789-F795 ◽  
Author(s):  
Margo P. Cohen ◽  
Gregory T. Lautenslager ◽  
Elizabeth Hud ◽  
Elizabeth Shea ◽  
Amy Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Insufficiency ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Glycated Albumin ◽  
Extracellular Matrix Protein ◽  
Type Iv ◽  
Endothelial Growth Factor ◽  
Tgf Β1

Glomerular cells in culture respond to albumin containing Amadori glucose adducts (the principal serum glycated protein), with activation of protein kinase C-β1, increased expression of transforming growth factor (TGF)-β1, the TGF-β type II signaling receptor, and the extracellular matrix proteins α1(IV) collagen and fibronectin and with decreased production of the podocyte protein nephrin. Decreasing the burden of glycated albumin in diabetic db/db mice significantly reduces glomerular overexpression of TGF-β1 mRNA, restores glomerular nephrin immunofluorescence, and lessens proteinuria, mesangial expansion, renal extracellular matrix protein production, and increased glomerular vascular endothelial growth factor (VEGF) immunostaining. In the present study, db/db mice were treated with a small molecule, designated 23CPPA, that inhibits the nonenzymatic condensation of glucose with the albumin protein to evaluate whether increased glycated albumin influences the production of VEGF receptors (VEGFRs) and type IV collagen subchains and ameliorates the development of renal insufficiency. Renal levels of VEGF and VEGFR-1 proteins and serum creatinine concentrations were significantly higher and renal levels of α3(IV) collagen and nephrin proteins and endogenous creatinine clearance values were significantly lower in control diabetic than in age-matched nondiabetic ( db/m) mice. These changes were significantly attenuated in db/db littermate mice treated from 9 to 18 wk of age with 23CPPA. The findings indicate that inhibiting excess nonenzymatic glycation of serum albumin improves renal molecular biology abnormalities and protects against the development of renal insufficiency in the db/db mouse.

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