Formation of corneal endothelium is essential for anterior segment development - a transgenic mouse model of anterior segment dysgenesis

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 533-542
Author(s):  
L.W. Reneker ◽  
D.W. Silversides ◽  
L. Xu ◽  
P.A. Overbeek
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Corneal Epithelium ◽  
Corneal Endothelium ◽  
Transforming Growth Factor ◽  
Anterior Segment ◽  
Corneal Stroma ◽  
Corneal Opacity ◽  
Cell Types ◽  
Surface Ectoderm

The anterior segment of the vertebrate eye is constructed by proper spatial development of cells derived from the surface ectoderm, which become corneal epithelium and lens, neuroectoderm (posterior iris and ciliary body) and cranial neural crest (corneal stroma, corneal endothelium and anterior iris). Although coordinated interactions between these different cell types are presumed to be essential for proper spatial positioning and differentiation, the requisite intercellular signals remain undefined. We have generated transgenic mice that express either transforming growth factor (alpha) (TGF(alpha)) or epidermal growth factor (EGF) in the ocular lens using the mouse (alpha)A-crystallin promoter. Expression of either growth factor alters the normal developmental fate of the innermost corneal mesenchymal cells so that these cells often fail to differentiate into corneal endothelial cells. Both sets of transgenic mice subsequently manifest multiple anterior segment defects, including attachment of the iris and lens to the cornea, a reduction in the thickness of the corneal epithelium, corneal opacity, and modest disorganization in the corneal stroma. Our data suggest that formation of a corneal endothelium during early ocular morphogenesis is required to prevent attachment of the lens and iris to the corneal stroma, therefore permitting the normal formation of the anterior segment.

scholarly journals Mammary Carcinogenesis Is Preceded by Altered Epithelial Cell Turnover in Transforming Growth Factor-α and c-myc Transgenic Mice

2006 ◽  
Vol 169 (5) ◽  
pp. 1821-1832 ◽  
Author(s):  
Teresa A. Rose-Hellekant ◽  
Kristin M. Wentworth ◽  
Sarah Nikolai ◽  
Donald W. Kundel ◽  
Eric P. Sandgren
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Mammary Carcinogenesis ◽  
Cell Turnover ◽  
Transforming Growth Factor Α ◽  
Factor Α

Transforming growth factor-? isoforms differently stimulate pro?2 (I) collagen gene expression during wound healing process in transgenic mice

2002 ◽  
Vol 190 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Takuro Kinbara ◽  
Fumiaki Shirasaki ◽  
Shigeru Kawara ◽  
Yutaka Inagaki ◽  
Benoit de Crombrugghe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Wound Healing Process ◽  
Collagen Gene ◽  
Collagen Gene Expression

scholarly journals Transforming Growth Factor β-Mediated Transcriptional Repression of c-myc Is Dependent on Direct Binding of Smad3 to a Novel Repressive Smad Binding Element

2004 ◽  
Vol 24 (6) ◽  
pp. 2546-2559 ◽  
Author(s):  
Joshua P. Frederick ◽  
Nicole T. Liberati ◽  
David S. Waddell ◽  
Yigong Shi ◽  
Xiao-Fan Wang
Keyword(s):  
Growth Factor ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Specific Cell ◽  
Smad Proteins ◽  
Smad Binding Element

ABSTRACT Smad proteins are the most well-characterized intracellular effectors of the transforming growth factor β (TGF-β) signal. The ability of the Smads to act as transcriptional activators via TGF-β-induced recruitment to Smad binding elements (SBE) within the promoters of TGF-β target genes has been firmly established. However, the elucidation of the molecular mechanisms involved in TGF-β-mediated transcriptional repression are only recently being uncovered. The proto-oncogene c-myc is repressed by TGF-β, and this repression is required for the manifestation of the TGF-β cytostatic program in specific cell types. We have shown that Smad3 is required for both TGF-β-induced repression of c-myc and subsequent growth arrest in keratinocytes. The transcriptional repression of c-myc is dependent on direct Smad3 binding to a novel Smad binding site, termed a repressive Smad binding element (RSBE), within the TGF-β inhibitory element (TIE) of the c-myc promoter. The c-myc TIE is a composite element, comprised of an overlapping RSBE and a consensus E2F site, that is capable of binding at least Smad3, Smad4, E2F-4, and p107. The RSBE is distinct from the previously defined SBE and may partially dictate, in conjunction with the promoter context of the overlapping E2F site, whether the Smad3-containing complex actively represses, as opposed to transactivates, the c-myc promoter.

scholarly journals Transforming growth factor–β in tissue fibrosis

2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Nikolaos G. Frangogiannis
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cellular Targets ◽  
Extracellular Matrix Molecules ◽  
Interacting Networks

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β–driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

scholarly journals Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Valentin Platel ◽  
Sébastien Faure ◽  
Isabelle Corre ◽  
Nicolas Clere
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Therapy Resistance ◽  
Experimental Conditions ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

Cancer cells evolve in a very complex tumor microenvironment, composed of several cell types, among which the endothelial cells are the major actors of the tumor angiogenesis. Today, these cells are also characterized for their plasticity, as endothelial cells have demonstrated their potential to modify their phenotype to differentiate into mesenchymal cells through the endothelial-to-mesenchymal transition (EndoMT). This cellular plasticity is mediated by various stimuli including transforming growth factor-β (TGF-β) and is modulated dependently of experimental conditions. Recently, emerging evidences have shown that EndoMT is involved in the development and dissemination of cancer and also in cancer cell to escape from therapeutic treatment. In this review, we summarize current updates on EndoMT and its main induction pathways. In addition, we discuss the role of EndoMT in tumorigenesis, metastasis, and its potential implication in cancer therapy resistance.

Dose-dependent lung remodeling in transgenic mice expressing transforming growth factor-α

2001 ◽  
Vol 281 (5) ◽  
pp. L1088-L1094 ◽  
Author(s):  
William D. Hardie ◽  
Alyssa Piljan-Gentle ◽  
Michelle R. Dunlavy ◽  
Machiko Ikegami ◽  
Thomas R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Proliferating Cells ◽  
Transforming Growth Factor Α ◽  
Lung Remodeling ◽  
Transgenic Lines ◽  
Factor Α ◽  
Dose Dependent

Transgenic mice overexpressing human transforming growth factor-α (TGF-α) develop emphysema and fibrosis during postnatal alveologenesis. To assess dose-related pulmonary alterations, four distinct transgenic lines expressing different amounts of TGF-α in the distal lung under control of the surfactant protein C (SP-C) promoter were characterized. Mean lung homogenate TGF-α levels ranged from 388 ± 40 pg/ml in the lowest expressing line to 1,247 ± 33 pg/ml in the highest expressing line. Histological assessment demonstrated progressive alveolar airspace size changes that were more severe in the higher expressing TGF-α lines. Pleural and parenchymal fibrosis were only detected in the highest expressing line ( line 28), and increasing terminal airspace area was associated with increasing TGF-α expression. Hysteresis on pressure-volume curves was significantly reduced in line 28 mice compared with other lines of mice. There were no differences in bronchoalveolar lavage fluid cell count or differential that would indicate any evidence of lung inflammation among all transgenic lines. Proliferating cells were increased in line 28 without alterations of numbers of type II cells. We conclude that TGF-α lung remodeling in transgenic mice is dose dependent and is independent of pulmonary inflammation.

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