Overexpression of SIK2 Inhibits FGF2-dependent Müller Glial Reprogramming

Abstract

Objective: Upon injury, Müller cells re-enter the cell cycle, acquire progenitor properties, and produce new retinal neurons in zebrafish. Proliferation is an essential step in retinal regeneration. The strict regulation of Müller cell proliferation limits mammalian retinal regeneration. Growth factors such as fibroblast growth factor 2 (FGF2) can promote the proliferation of Müller glia in mammals; however, the regeneration capacity is restricted. In this study, we investigated the possible contribution of salt-inducible kinase 2 (SIK2) to Müller reprogramming through FGF2 signaling. Materials and Methods: MIO-M1 cells were used as the model system. Modulations in cell proliferation, extracellular signal-regulated kinase (ERK)1/2 activity, and SIK2 expression during 7 days of FGF2 treatment were documented. Overexpression studies were conducted to provide clues for the potential contribution of SIK2 to MIO-M1 reprogramming. Results: Our findings demonstrate that the expansion of Müller cells that de-differentiate into progenitors requires ERK activation. A significant reduction in the SIK2 protein level is necessary for Müller cells to proliferate. SIK2 overexpression inhibited ERK activity, cell proliferation, and reprogramming. Conclusion: We propose that SIK2 is involved in Müller reprogramming by suppressing ERK activation.

Keywords

• SIK2
• FGF2
• ERK
• Reprogramming
• Müller glia

References

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