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

doi:10.1016/j.celrep.2021.109866

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

School of Medicine

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	109866
Journal	Cell Reports
Volume	37
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2021.109866
State	Published - 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

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2021.109866

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

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.",

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

author = "Mertz, {Joseph L.} and Sripathi, {Srinivasa R.} and Xue Yang and Lijun Chen and Noriko Esumi and Hui Zhang and Zack, {Donald J.}",

note = "Funding Information: We gratefully acknowledge generous funding from the Maryland Stem Cell Research Fund , the Knights Templar Eye Foundation , the Edward N. and Della L. Thome Memorial Foundation , Research to Prevent Blindness , the Bright-Focus Foundation , the NIH ( P30EY001765 ), and the Guerrieri Family Foundation . Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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doi = "10.1016/j.celrep.2021.109866",

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AU - Mertz, Joseph L.

AU - Sripathi, Srinivasa R.

AU - Yang, Xue

AU - Chen, Lijun

AU - Esumi, Noriko

AU - Zhang, Hui

AU - Zack, Donald J.

N1 - Funding Information: We gratefully acknowledge generous funding from the Maryland Stem Cell Research Fund , the Knights Templar Eye Foundation , the Edward N. and Della L. Thome Memorial Foundation , Research to Prevent Blindness , the Bright-Focus Foundation , the NIH ( P30EY001765 ), and the Guerrieri Family Foundation . Publisher Copyright: © 2021 The Author(s)

PY - 2021/10/19

Y1 - 2021/10/19

N2 - 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.

AB - 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.

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KW - TGF-β

KW - TNF-α

KW - epithelial-mesenchymal translation

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KW - phosphoproteomics

KW - proteomics

KW - retinal pigment epithelium

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

Abstract

Keywords

ASJC Scopus subject areas

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