Abstract Title
Differential Regulation of Snail and Slug Transcription Factors During TGFÎ2 Induced Tenogenic Differentiation
Additional Funding Sources
The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant No. P20GM103408.
Abstract
Tendons are frequently injured and have poor healing capacity. Current repair methods do not result in tendons with comparable strength to uninjured tendons. Therefore, there is a need to advance effective repairs for tendon injuries. Mesenchymal stem cells (MSCs) are currently being explored as one potential therapy. To improve stem cell therapies, a better understanding of the mechanisms that regulate differentiation toward the tendon lineage (tenogenesis) is needed. Previous work has shown that the cell-cell junction protein, N-cadherin, decreases during transforming growth factor (TGF)B2-induced tenogenesis in MSCs. However, it is unknown how N-cadherin is regulated during tenogenesis. Studies in other cell types and during epithelial-to-mesenchymal transition (EMT) suggest that the transcription factors, Snail and Slug, regulate levels of cadherins, but this has not been explored in tenogenesis. To address this missing detail, this study aimed to determine how Snail and Slug were regulated during TGFB2-induced tenogenesis in MSCs and how that related to N-cadherin levels. Western blotting was used to evaluate the levels of Snail and Slug in TGFB2 treated MSCs. Results show that Snail increased after one day of TGFB2 treatment, and then plateaued, while Slug consistently decreased with TGFB2 across all time points. N-cadherin levels were decreased at the same, thus indicating the possibility of Snail and Slug playing a role in regulating cadherins during tenogenesis.
Differential Regulation of Snail and Slug Transcription Factors During TGFÎ2 Induced Tenogenic Differentiation
Tendons are frequently injured and have poor healing capacity. Current repair methods do not result in tendons with comparable strength to uninjured tendons. Therefore, there is a need to advance effective repairs for tendon injuries. Mesenchymal stem cells (MSCs) are currently being explored as one potential therapy. To improve stem cell therapies, a better understanding of the mechanisms that regulate differentiation toward the tendon lineage (tenogenesis) is needed. Previous work has shown that the cell-cell junction protein, N-cadherin, decreases during transforming growth factor (TGF)B2-induced tenogenesis in MSCs. However, it is unknown how N-cadherin is regulated during tenogenesis. Studies in other cell types and during epithelial-to-mesenchymal transition (EMT) suggest that the transcription factors, Snail and Slug, regulate levels of cadherins, but this has not been explored in tenogenesis. To address this missing detail, this study aimed to determine how Snail and Slug were regulated during TGFB2-induced tenogenesis in MSCs and how that related to N-cadherin levels. Western blotting was used to evaluate the levels of Snail and Slug in TGFB2 treated MSCs. Results show that Snail increased after one day of TGFB2 treatment, and then plateaued, while Slug consistently decreased with TGFB2 across all time points. N-cadherin levels were decreased at the same, thus indicating the possibility of Snail and Slug playing a role in regulating cadherins during tenogenesis.