scholarly journals Transforming Growth Factor-β Induces Transcription Factors MafK and Bach1 to Suppress Expression of the Heme Oxygenase-1 Gene

2013 ◽  
Vol 288 (28) ◽  
pp. 20658-20667 ◽  
Author(s):  
Yukari Okita ◽  
Atsushi Kamoshida ◽  
Hiroyuki Suzuki ◽  
Ken Itoh ◽  
Hozumi Motohashi ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Heme Oxygenase 1

scholarly journals Smad7-dependent Regulation of Heme Oxygenase-1 by Transforming Growth Factor-β in Human Renal Epithelial Cells

2000 ◽  
Vol 275 (52) ◽  
pp. 40904-40909 ◽  
Author(s):  
Nathalie Hill-Kapturczak ◽  
Leigh Truong ◽  
Vijayalakshmi Thamilselvan ◽  
Gary A. Visner ◽  
Harry S. Nick ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Heme Oxygenase 1 ◽  
Renal Epithelial Cells

Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-β1 in renal epithelial cells

2007 ◽  
Vol 293 (3) ◽  
pp. F885-F894 ◽  
Author(s):  
Amie Traylor ◽  
Thomas Hock ◽  
Nathalie Hill-Kapturczak
Keyword(s):  
Growth Factor ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Transforming Growth Factor Β1 ◽  
Molecular Regulation ◽  
Heme Oxygenase 1 ◽  
Specificity Protein 1 ◽  
Specificity Protein ◽  
Tgf Β1

Excess transforming growth factor-β1 (TGF-β1) in the kidney leads to increased cell proliferation and deposition of extracellular matrix, resulting in progressive kidney fibrosis. TGF-β1, however, stabilizes and attenuates tissue injury through the activation of cytoprotective proteins, including heme oxygenase-1 (HO-1). HO-1 catabolizes pro-oxidant heme into substances with anti-oxidant, anti-apoptotic, anti-fibrogenic, vasodilatory and immune modulatory properties. Little is known regarding the molecular regulation of human HO-1 induction by TGF-β1 except that it is dependent on de novo RNA synthesis and requires a group of structurally related proteins called Smads. It is not known whether other DNA binding proteins are required to initiate transcription of HO-1 and, furthermore, the promoter region(s) involved in TGF-β1-mediated induction of HO-1 has not been identified. The purpose of this study was to further delineate the molecular regulation of HO-1 by TGF-β1 in human renal proximal tubular cells. Actinomycin D and nuclear run-on studies demonstrate that TGF-β1 augments HO-1 expression by increased gene transcription and does not involve increased mRNA stability. Using transient transfection, mithramycin A, small interfering RNA, electrophoretic mobility shift assays, and decoy oligonucleotide experiments, a TGF-β1-responsive region is identified between 9.1 and 9.4 kb of the human HO-1 promoter. This ∼280-bp TGF-β1-responsive region contains a putative Smad binding element and specificity protein 1 binding sites, both of which are required for human HO-1 induction by TGF-β1.

scholarly journals Transforming growth factor β1 enhances heme oxygenase 1 expression in human synovial fibroblasts by inhibiting microRNA 519b synthesis

PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0176052 ◽  
Author(s):  
Shu-Jui Kuo ◽  
Wei-Hung Yang ◽  
Shan-Chi Liu ◽  
Chun-Hao Tsai ◽  
Horng-Chaung Hsu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Transforming Growth Factor Β1 ◽  
Heme Oxygenase 1

scholarly journals Synergism between Transcription Factors TFE3 and Smad3 in Transforming Growth Factor-β-induced Transcription of theSmad7Gene

2000 ◽  
Vol 275 (43) ◽  
pp. 33205-33208 ◽  
Author(s):  
Xianxin Hua ◽  
Zachary A. Miller ◽  
Hassina Benchabane ◽  
Jeffrey L. Wrana ◽  
Harvey F. Lodish
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Induction of Heme Oxygenase-1 During Endotoxemia Is Downregulated by Transforming Growth Factor-β1

1998 ◽  
Vol 83 (4) ◽  
pp. 396-403 ◽  
Author(s):  
Andrea Pellacani ◽  
Philippe Wiesel ◽  
Arunabh Sharma ◽  
Lauren C. Foster ◽  
Gordon S. Huggins ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Heme Oxygenase 1

scholarly journals Recognition of Phosphorylated-Smad2-Containing Complexes by a Novel Smad Interaction Motif

2004 ◽  
Vol 24 (3) ◽  
pp. 1106-1121 ◽  
Author(s):  
Rebecca A. Randall ◽  
Michael Howell ◽  
Christopher S. Page ◽  
Amanda Daly ◽  
Paul A. Bates ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Hydrophobic Pocket ◽  
Winged Helix ◽  
The Common ◽  
Necessary And Sufficient

ABSTRACT Transforming growth factor β (TGF-β) superfamily members signal via complexes of activated Smads, comprising phosphorylated receptor-regulated Smads, such as Smad2 and Smad3, and Smad4. These complexes are recruited to DNA by specific transcription factors. The forkhead/winged-helix transcription factors, XFast-1/XFoxH1a and XFast-3/XFoxH1b, bind an activated Smad heterotrimer comprising two Smad2s and one Smad4. Here we identify a novel Smad2 interaction motif, the Fast/FoxH1 motif (FM), present in all known Fast/FoxH1 family members, N-terminal to the common Smad interaction motif (SIM). The FM is necessary and sufficient to bind active Smad2/Smad4 complexes. The FM differs from the SIM since it discriminates between Smad2 and Smad3, and moreover only binds phosphorylated Smad2 in the context of activated Smad complexes. It is the first Smad interaction motif with this property. Site-directed mutagenesis indicates that the binding site for the FM on a Smad2/Smad4 heterotrimer is a hydrophobic pocket that incorporates the Smad/Smad interface. We demonstrate that the presence of an FM and SIM in the Fast/FoxH1 proteins allows them to compete efficiently for activated Smad2/Smad4 complexes with transcription factors such as Mixer that only contain a SIM. This establishes a hierarchy of Smad-interacting transcription factors, determined by their affinity for active Smad complexes.

scholarly journals NFI-Ski Interactions Mediate Transforming Growth Factor β Modulation of Human Papillomavirus Type 16 Early Gene Expression

2004 ◽  
Vol 78 (8) ◽  
pp. 3953-3964 ◽  
Author(s):  
Amy Baldwin ◽  
Lucia Pirisi ◽  
Kim E. Creek
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Growth Factor ◽  
Binding Sites ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Early Gene ◽  
Early Gene Expression ◽  
Nuclear Extracts ◽  
E6 And E7

ABSTRACT Human papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor β (TGF-β). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-β. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-β modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-β modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-β-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-β. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-β treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-β sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-β to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-β treatment, we explored the possibility that Ski may provide a link between TGF-β signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI and Ski interact in these cells. Ski levels dramatically decreased upon TGF-β treatment of HKc/HPV16, and overexpression of Ski eliminated the ability of TGF-β to inhibit the URR. Based on these studies, we propose that TGF-β inhibition of HPV16 early gene expression is mediated by a decrease in Ski levels, which in turn dramatically reduces NFI activity.

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