Glucocorticosteroids up-regulate human elastin gene promoter activity in transgenic mice

Area of Science:

• Molecular Biology
• Genetics
• Endocrinology

Background:

• The human elastin gene's 5'-flanking DNA contains three potential glucocorticoid responsive elements (GREs).
• Understanding the regulation of elastin production is crucial for tissue development and repair.

Purpose of the Study:

• To investigate the functional activity of putative glucocorticoid responsive elements (GREs) in the human elastin gene.
• To determine the effect of glucocorticosteroids on human elastin gene promoter activity in vivo and in vitro.

Main Methods:

• Generation of transgenic mice harboring a human elastin promoter-reporter gene (CAT) construct.
• Administration of glucocorticosteroids (triamcinolone acetonide and dexamethasone) via subcutaneous and intraperitoneal injection.
• Assay of CAT activity in skin, internal organs, and cultured cells (fibroblasts and aortic smooth muscle cells).

Main Results:

• Subcutaneous glucocorticoid injection enhanced CAT activity in mouse skin by up to 28-fold.
• Intraperitoneal dexamethasone administration increased elastin promoter activity in various internal organs.
• In vitro incubation with triamcinolone acetonide markedly increased elastin promoter activity in cultured skin fibroblasts and aortic smooth muscle cells.

Conclusions:

• Glucocorticosteroids act as potent up-regulators of human elastin promoter activity.
• The identified GREs are functional and mediate glucocorticoid-induced elastin gene expression.
• These findings provide evidence for the role of glucocorticoids in controlling elastin synthesis.