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Published on: August 20, 2016
The role of Wnt/β-catenin pathway for skin-derived precursors differentiating into corneal endothelial cell-like
Lin Shen1, Lijie Pan2, Chengqun Ju3
1Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Laboratory of Basic Medical Science, Qilu Hospital, Shandong University.
Abstract:
Bullous keratopathy is a serious blinding eye disease requiring corneal endothelial transplantation. However, the lack of cornea donors forced us to search for new sources of functional corneal endothelial cells (CECs). In our previous study, we have successfully differentiated the SKPs into CEC-like cells with unclear mechanism. The Wnt/β-catenin signaling pathway is essential for maintaining embryonic eye development and formation. This study aimed to clarify the activity of Wnt/β-catenin pathway in the process of skin-derived precursors (SKPs) differentiating into CEC-like cells. We showed that the expression of active β-Catenin, p-GSK3β, P-LRP6 and LRP6 upregulated, indicating the activation of Wnt/β-catenin pathway during CEC-like cells induction. What's more, when the pathway was inhibited with a specific inhibitor, the process of induction was obviously suppressed. These findings indicates that Wnt/β-catenin pathway plays an important role in the CEC-like cells induction from SKPs. Our study lays an experimental foundation for providing abundant corneal endothelial cells and promotes CEC-like cells to be clinically applied in cellular replacement therapy or regenerative medicine in the future.
Insights
Skin-derived precursors (SKPs) can become corneal endothelial-like cells (CECs) through Wnt/β-catenin pathway activation. Inhibiting this pathway suppressed CEC-like cell induction, highlighting its crucial role in generating cells for eye repair.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Cell Biology
Background:
- Bullous keratopathy necessitates corneal endothelial transplantation.
- A shortage of donor corneas drives the search for alternative sources of corneal endothelial cells (CECs).
- Previous work demonstrated skin-derived precursors (SKPs) can differentiate into CEC-like cells, but the mechanism was unclear.
Purpose of the Study:
- To elucidate the role of the Wnt/β-catenin signaling pathway in the differentiation of SKPs into CEC-like cells.
- To investigate the mechanism underlying SKP differentiation into functional CECs.
Main Methods:
- Monitoring the expression of key Wnt/β-catenin pathway components (active β-Catenin, p-GSK3β, P-LRP6, LRP6) during SKP differentiation.
- Utilizing a specific Wnt/β-catenin pathway inhibitor to assess its impact on CEC-like cell induction.
Main Results:
- Upregulation of active β-Catenin, p-GSK3β, P-LRP6, and LRP6 confirmed Wnt/β-catenin pathway activation during CEC-like cell induction.
- Inhibition of the Wnt/β-catenin pathway significantly suppressed the differentiation process.
- These findings demonstrate the pathway's critical involvement in generating CEC-like cells from SKPs.
Conclusions:
- The Wnt/β-catenin signaling pathway is essential for inducing corneal endothelial-like cells from skin-derived precursors.
- This research provides a foundation for generating abundant CECs for potential clinical applications in cellular replacement therapy and regenerative medicine for blinding eye diseases.
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