The complicated problem of efficient stimulation of elastic fiber production in already developed human tissues has not yet been solved. The present study introduces sodium ascorbate (SA) as a stimulator of elastogenesis in cultures of different cell types including fibroblasts isolated from patients with elastopathy genetic diseases. We then elucidated mechanisms of elastogenic action of SA. SA exercises its net elastogenic effect only after being actively transported into the cell interior through two separate mechanisms. These are the “fast effect,” which reflects the greater stability of intracellular tropoelastin, and the “late effect,” which reflects the true enhancement of the elastin gene expression occurring after SA-induced activation of c-src tyrosine kinase and the consecutive phosphorylation of IGF-1 receptor, which triggers the downstream signals leading to activation of the elastin gene expression. In conclusion, for the first time we have established that SA is a potent stimulator of elastic fiber production.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30119 |
| Date | 30 November 2011 |
| Creators | Hyunjun, Kim |
| Contributors | Hinek, Aleksander |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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