scholarly journals Gonadotropin Releasing Hormone and Transforming Growth Factor β Activate Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase and Differentially Regulate Fibronectin, Type I Collagen, and Plasminogen Activator Inhibitor-1 Expression in Leiomyoma and Myometrial Smooth Muscle Cells

2004 ◽  
Vol 89 (11) ◽  
pp. 5549-5557 ◽  
Author(s):  
Li Ding ◽  
Jingxia Xu ◽  
Xiaoping Luo ◽  
Nasser Chegini
Keyword(s):  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mitogen Activated Protein ◽  
Activator Inhibitor ◽  
Fibronectin Type

scholarly journals Histone Deacetylase Inhibitor Impairs Plasminogen Activator Inhibitor-1 Expression via Inhibiting TNF-α-Activated MAPK/AP-1 Signaling Cascade

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Wei-Lin Chen ◽  
Joen-Rong Sheu ◽  
Che-Jen Hsiao ◽  
Shih-Hsin Hsiao ◽  
Chi-Li Chung ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Histone Deacetylases ◽  
Plasminogen Activator Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Hdac Inhibition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Hdac Activity ◽  
Mitogen Activated Protein ◽  
Activator Inhibitor ◽  
Pai 1

Tumor necrosis factor-(TNF-)-αupregulates plasminogen activator inhibitor-(PAI-) 1 expression in pleural mesothelial cells (PMCs), contributing to fibrin deposition and pleural fibrosis. Histone deacetylases (HDACs) have been found implicated in fibrogenesis. However, the roles of TNF-αor HDAC in the regulation of PAI-1 expression have not been well investigated. We aimed to examine the effects and mechanisms of HDAC inhibition on TNF-α-induced PAI-1 expression in human PMCs. MeT-5A human PMCs were treated with TNF-αin the presence or absence of them-carboxycinnamic acid bishydroxamide (CBHA), an HDAC class II inhibitor, and the HDAC activity, PAI-1 protein expression, mRNA, and activated signalings were analyzed. CBHA abrogated TNF-α-induced HDAC activity, PAI-1 protein and, mRNA expression in MeT-5A cells. Moreover, CBHA significantly enhanced mitogen-activated protein kinase phosphatase-(MKP-) 5/MKP-1 expression and inhibited p38/JNK activations, ATF2/c-Jun translocation, and PAI-1 promoter activity. Altogether, our data suggest that HDAC inhibition may abrogate TNF-α-activated MAPK/AP-1 signaling and PAI-1 expression in human PMCs. Given the antifibrotic effect through PAI-1 abrogation, CBHA may be utilized as a novel agent in the treatment of fibrotic diseases.

scholarly journals High doses of TGF-β potently suppress type I collagen via the transcription factor CUX1

2011 ◽  
Vol 22 (11) ◽  
pp. 1836-1844 ◽  
Author(s):  
Maria Fragiadaki ◽  
Tetsurou Ikeda ◽  
Abigail Witherden ◽  
Roger M Mason ◽  
David Abraham ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Aberrant Expression

Transforming growth factor-β (TGF-β) is an inducer of type I collagen, and uncontrolled collagen production leads to tissue scarring and organ failure. Here we hypothesize that uncovering a molecular mechanism that enables us to switch off type I collagen may prove beneficial in treating fibrosis. For the first time, to our knowledge, we provide evidence that CUX1 acts as a negative regulator of TGF-β and potent inhibitor of type I collagen transcription. We show that CUX1, a CCAAT displacement protein, is associated with reduced expression of type I collagen both in vivo and in vitro. We show that enhancing the expression of CUX1 results in effective suppression of type I collagen. We demonstrate that the mechanism by which CUX1 suppresses type I collagen is through interfering with gene transcription. In addition, using an in vivo murine model of aristolochic acid (AA)-induced interstitial fibrosis and human AA nephropathy, we observe that CUX1 expression was significantly reduced in fibrotic tissue when compared to control samples. Moreover, silencing of CUX1 in fibroblasts from kidneys of patients with renal fibrosis resulted in increased type I collagen expression. Furthermore, the abnormal CUX1 expression was restored by addition of TGF-β via the p38 mitogen-activated protein kinase pathway. Collectively, our study demonstrates that modifications of CUX1 expression lead to aberrant expression of type I collagen, which may provide a molecular basis for fibrogenesis.

scholarly journals Dietary Suberic Acid Protects Against UVB-Induced Skin Photoaging in Hairless Mice

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2948 ◽  
Author(s):  
Wesuk Kang ◽  
Dabin Choi ◽  
Taesun Park
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Collagen Type I ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Activator Protein 1 ◽  
Suberic Acid ◽  
Hairless Mice ◽  
Mitogen Activated Protein ◽  
Skin Photoaging

Ultraviolet (UV) radiation is a major cause of skin photoaging, which is mainly characterized by dryness and wrinkle formation. In the current study, we investigated the anti-photoaging effects of dietary suberic acid, a naturally occurring photochemical, using UVB-irradiated hairless mice. Mice were exposed to UVB three times weekly and fed diets containing three different suberic acid concentrations (0.05%, 0.1% and 0.2%) for 10 weeks. It was found that suberic acid inhibited UVB-induced skin dryness, wrinkle formation, and epidermal thickness in hairless mice. In parallel with phenotypic changes, suberic acid attenuated UVB-induced matrix metalloproteinase (MMP) genes (MMP1a, MMP1b, MMP3, and MMP9), while accelerating collagen genes including collagen type I alpha 1 chain (COL1A1), COL1A2, and COL3A1 and hyaluronic acid synthases genes (HAS1, HAS2 and HAS3). We further demonstrated that suberic acid upregulated the molecules involved in the transforming growth factor–β (TGF-β)/SMAD pathway, but downregulated the molecules participating in the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling in UVB-irritated hairless mice. Collectively, we propose that suberic acid may be a promising agent for treating skin photoaging.

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