| First Author | Liu B | Year | 2013 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 54 |
| Issue | 2 | Pages | 1061-9 |
| PubMed ID | 23329662 | Mgi Jnum | J:214928 |
| Mgi Id | MGI:5604216 | Doi | 10.1167/iovs.12-10142 |
| Citation | Liu B, et al. (2013) TGFbeta signaling induces expression of Gadd45b in retinal ganglion cells. Invest Ophthalmol Vis Sci 54(2):1061-9 |
| abstractText | PURPOSE: Growth arrest and DNA damage protein 45b (Gadd45b) functions as an intrinsic neuroprotective molecule protecting retinal ganglion cells (RGCs) from injury. This study was performed to elucidate further the induction pathway of Gadd45b expression in RGCs. METHODS: The induction of Gadd45b expression in response to TGFbetaNFkappaB signaling was investigated in RGC5 cultures in vitro and murine retina in vivo. Gadd45b mRNA and protein expression were detected by quantitative real-time RT-PCR, immunoblot assay, immunohistochemistry, and immunocytochemistry. Activation of NFkappaB and TGFbeta/Gadd45b signaling were assessed by measuring phosphorylation of NFkappaB and using specific inhibitors. Gadd45b siRNA was transfected into RGC5 to silence Gadd45b mRNA expression. RESULTS: Expression of TGFbeta receptors I and II was detected in RGC5 in vitro and RGCs in vivo. TGFbeta induced abundant Gadd45b mRNA and protein expression, exhibiting a dose-dependent response in vitro. Exogenous TGFbeta1 induced upregulation of Gadd45b expression in RGCs in murine retina in vivo. TGFbeta stimulated phosphorylation of NFkappaB, and inhibition of NFkappaB phosphorylation blocked induction of Gadd45b by TGFbeta in RGC5 cells. Induction of Gadd45b by TGFbeta increased the resistance of RGC5 cells against TNFalpha cytotoxicity and paraquat oxidative stress. CONCLUSIONS: TGFbeta signaling induced Gadd45b expression in RGCs. Modulation of the TGFbeta/NFkappaB/Gadd45b signaling pathway may provide a means to enhance the neuroprotective effect of Gadd45b in RGCs. |
