3,3′,5′-triido-L-thyronine alters protein kinase B, phosphotase and tensin homolog and connective tissue growth factor expression in human dermal fibroblasts
Gonzales, Christopher R
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Cutaneous tissue repair is complex and involves a variety of growth factors to regulate a balance of regeneration and fibrosis during healing. This process is divided into three sequential and overlapping phases: the inflammatory phase, the proliferative phase, and the remodeling phase. Fibroblasts are crucial during this process in that they help initiate inflammatory activity, deposit extracellular matrix proteins for granulation tissue and deconstruct granulation tissue to make way for mature scar formation. Previous studies on the effects of 3,3',5'-triiodo-L-thyronine (T3) on skin have revealed that healing tissue responds to T3 by accelerating skin cell proliferation and migration. These findings indicate that T3 offers potential as a therapeutic drug for individuals with extensive cutaneous damage, chronic skin maladies or retarded wound healing. The mechanisms underlying these changes are not clearly understood, however, elucidation of changes in protein expression patterns should be evaluated to appropriately judge the therapeutic potential of T3. This study aims to characterize T3 dose responsive expression of protein kinase B, phosphatase and tensin homolog, connective tissue growth factor and wnt5a. Western blot analysis and immunodetection revealed that wnt5a is not expressed in human dermal fibroblasts. Protein kinase B did not vary significantly with T3 concentration ranging from 1.0 nM-1.0 1µM, F(4,5)= 1.93, p > 0.05, nor did connective tissue growth factor, F(4,5) = 2.16, p > 0.05. In contrast, phosphatase and tensin homolog showed a statistically significant change in expression, F(4, 15) = 4.67, p less than 0.05. The results presented here provide insight into protein pathways and growth factors through which thyroid hormone produces its effects on the various cells of the integument and suggests that phosphatase and tensin homolog (PTEN) expression levels are responsive to varying concentrations of T3. Future studies should further evaluate the role of T3 on its various targets as a therapeutic option for skin disorders.
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