Proteomic and phosphoproteomic analyses identify liver-related signaling in retinal pigment epithelial cells during EMT

Joseph L. Mertz, Srinivasa R. Sripathi, Xue Yang, Lijun Chen, Noriko Esumi, Hui Zhang, Donald J. Zack

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is associated with several blinding retinal diseases. Using proteomics and phosphoproteomics studies of human induced pluripotent stem cell-derived RPE monolayers with induced EMT, we capture kinase/phosphatase signaling cascades 1 h and 12 h after induction to better understand the pathways mediating RPE EMT. Induction by co-treatment with transforming growth factor β and tumor necrosis factor alpha (TGNF) or enzymatic dissociation perturbs signaling in many of the same pathways, with striking similarity in the respective phosphoproteomes at 1 h. Liver hyperplasia and hepatocyte growth factor (HGF)-MET signaling exhibit the highest overall enrichment. We also observe that HGF and epidermal growth factor signaling, two cooperative pathways inhibited by EMT induction, regulate the RPE transcriptional profile.

Original languageEnglish (US)
Article number109866
JournalCell Reports
Volume37
Issue number3
DOIs
StatePublished - Oct 19 2021

Keywords

  • EGF
  • HGF
  • TGF-β
  • TNF-α
  • epithelial-mesenchymal translation
  • human induced pluripotent stem cells
  • phosphoproteomics
  • proteomics
  • retinal pigment epithelium

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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