[Frontiers in Bioscience S1, 420-436, June 1, 2009]

[Frontiers in Bioscience S1, 420-436, June 1, 2009]

The FOX transcription factors regulate vascular pathology, diabetes and Tregs

Xiao-Feng Yang, Pu Fang,Shu Meng, Michael Jan, Xinyu Xiong, Ying Yin, Hong Wang

Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine,Philadelphia, PA 19140

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Overview of the FOX transcription factor superfamily: 3.1. Structure; 3.2. Expression; 3.3. Functional modes of FOX transcription factors; 3.4. Combinatorial regulation of gene expression by FOX transcription factors and other transcription factors; 3.5. Post-translational modification
4. Vascular pathology of mice deficient in FOX transcription factors
5. Roles of FOX transcription factors in endothelial cell pathology: 5.1. Endothelial apoptosis; 5.2. EPC apoptosis and maturation; 5.3. Endothelial cell proliferation; 5.4. Roles of FOX transcription factors in VEGF signaling; 5.5. Endothelial responses to stress; 5.6. Neovascularization
6. Roles of FOX transcription factors in vascular smooth muscle cells (VSMCs): 6.1. VSMC apoptosis; 6.2. VSMC proliferation; 6.3. FoxO in VSMC differentiation; 6.4. FoxO in aging VSMCs; 6.5. Roles of other FOX transcription factors in VSMCs
7. Roles of FOX transcription factors in the pathogenesis of diabetes: 7.1. FoxO and diabetes; 7.2. FoxO, EPC and diabetes; 7.3. FoxO and energy metabolism
8. Immune system phenotypes of mice deficient in FOX transcription factors: 8.1. FOX transcription factors and inflammation; 8.2. FoxP3, regulatory T cells and immune suppression; 8.3. FoxN1 and thymocyte development; 8.4. FOX transcription factors and T cell activation
9. Conclusion
10. References

1. ABSTRACT

A small number of upstream master genes in "higher hierarchy" controls the expression of a large number of downstream genes and integrates the signaling pathways underlying the pathogenesis of cardiovascular diseases with or without autoimmune inflammatory mechanisms. In this brief review, we organize our analysis of recent progress in characterization of forkhead (FOX) transcription factor family members in vascular pathology, diabetes and regulatory T cells into the following sections: (1) Overview of the FOX transcription factor superfamily; (2) Vascular pathology of mice deficient in FOX transcription factors; (3) Roles of FOX transcription factors in endothelial cell pathology; (4) Roles of FOX transcription factors in vascular smooth muscle cells; (5) Roles of FOX transcription factors in the pathogenesis of diabetes; and (6) Immune system phenotypes of mice deficient in FOX transcription factors. Advances in these areas suggest that the FOX transcription factor family plays important roles in vascular development and in the pathogenesis of autoimmune inflammatory cardiovascular diseases.