Transdifferentiation effects and related mechanisms of nerve growth factor and internal limiting membrane on M üller cells.

In this study, we investigated the pro-proliferative, pro-transdifferentiation effects and mechanisms of nerve growth factor (NGF), internal limiting membrane (ILM), and NGF+ILM on Müller cells. The Müller cells cultured with NGF, ILM or both were mediated with tyrosine kinase A (TrkA) (a high affinity receptor for NGF) inhibitor, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) (an intracellular signaling pathway important in regulating the cell cycle) inhibitor, or LIN28 (a RNA-binding protein and a posttranscriptional regulator of genes involved in developmental timing and self-renewal in embryonic stem cells) siRNA. Immunofluorescence (IF), western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of related genes. As a result, NGF, ILM and NGF+ILM promoted cell proliferation, increased the ratio of 5-bromo-2-deoxyuridine (BrdU)-positive cells, and were correlated with TrkA and PI3K/Akt signaling. NGF alone promoted cell dedifferentiation and redifferentiation mainly towards neurons rather than towards glial cells, related to TrkA and PI3K/Akt signals. The expression of p-Akt and cyclinD1 was increased by the intervention of NGF, ILM or NGF+ILM via TrkA and PI3K/Akt signals. NGF alone promoted the expression of paired box 6 (PAX6) (a transcription factor present during embryonic development), sex-determining region Y-box 2 (SOX2) (a transcription factor essential for the self-renewal, or pluri...
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research