Overexpression of SIK2 Inhibits FGF2-dependent Müller Glial Reprogramming

Abstract

Objective: Upon injury, M & uuml;ller 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 M & uuml;ller cell proliferation limits mammalian retinal regeneration. Growth factors such as fibroblast growth factor 2 (FGF2) can promote the proliferation of M & uuml;ller glia in mammals; however, the regeneration capacity is restricted. In this study, we investigated the possible contribution of salt-inducible kinase 2 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 M & uuml;ller cells that de-differentiate into progenitors requires ERK activation. A significant reduction in the SIK2 protein level is necessary for M & uuml;ller cells to proliferate. SIK2 overexpression inhibited ERK activity, cell proliferation, and reprogramming. Conclusion: We propose that SIK2 is involved in M & uuml;ller reprogramming by suppressing ERK activation.