Proteomic and phosphoproteomic analysis identifies novel liver-related signaling in retinal pigment epithelial cells during epithelial-mesenchymal transition

ABSTRACT: Epithelial–mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is associated with several potentially blinding retinal diseases. Proteomic and phosphoproteomic studies were performed on human induced pluripotent stem cell-derived RPE (hiPSC-RPE) monolayers to better understand the pathways mediating RPE EMT. EMT was induced by enzymatic dissociation of RPE monolayers from their culture substrate or by co-treatment with transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α) (TGNF). The proteome and phosphoproteome were analyzed at 1 hr post EMT induction to capture early events in kinase/phosphatase signaling cascades and at 12 hrs to define early changes in protein abundance. Pathway enrichment analysis revealed that TGNF and dissociation rapidly perturbed signaling in many of the same pathways, with striking similarity in the phosphoproteome at 1 hr. Surprisingly, functions related to liver cell proliferation and hyperplasia were strongly enriched in the phosphosites altered by both treatments at 1 hr and in protein abundance changes at 12 hrs. Hepatocyte Growth Factor-cMET signaling exhibited the strongest overall enrichment in both treatments. These signaling pathways may serve as suitable targets for the development of therapeutic strategies for the inhibition of RPE EMT, and thus may be targets for inhibiting progression of several debilitating visual diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Retinal Pigment Epithelial Cell, Retinal Pigment Epithelium Cell

SUBMITTER: Joseph Mertz  

LAB HEAD: Hui Zhang

PROVIDER: PXD020202 | Pride | 2021-11-03

REPOSITORIES: Pride