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PMID:21912637
| Citation |
Li, R, Wen, R, Banzon, T, Maminishkis, A and Miller, SS (2011) CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. PLoS ONE 6:e23148 |
|---|---|
| Abstract |
Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase). CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J(V)) across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease. |
| Links |
PubMed PMC3166283 Online version:10.1371/journal.pone.0023148 |
| Keywords |
Absorption; Body Fluids/metabolism; Cell Membrane/metabolism; Cell Polarity; Cell Proliferation; Cell Survival; Cells, Cultured; Ciliary Neurotrophic Factor/metabolism; Ciliary Neurotrophic Factor/secretion; Fetus/cytology; Gene Expression Regulation; Humans; Leukemia Inhibitory Factor/genetics; Leukemia Inhibitory Factor/secretion; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Oncostatin M/genetics; Oncostatin M/secretion; Organic Cation Transporter 1/genetics; Phagocytosis; Phosphorylation; Protein Subunits/metabolism; Protein Transport; Receptor, Ciliary Neurotrophic Factor/metabolism; Retinal Pigment Epithelium/cytology; Retinal Pigment Epithelium/metabolism; Retinal Pigment Epithelium/secretion; STAT3 Transcription Factor/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0003406: retinal pigment epithelium development |
ECO:0000314: |
P |
Figure 4 - states Constitutive expression of CNTF in human RPE. |
complete | ||||
| GO:0042517: positive regulation of tyrosine phosphorylation of Stat3 protein |
ECO:0000314: |
P |
Figure 6 - shows CNTF positive regulation of STAT3 phosphorylation. |
complete | ||||
|
involved_in |
GO:0042531: positive regulation of tyrosine phosphorylation of STAT protein |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0042517: positive regulation of tyrosine phosphorylation of Stat3 protein |
ECO:0000314: |
P |
Figure 6 - OsM shows positive regulation of STAT3 phosphorylation. |
complete | ||||
|
involved_in |
GO:0042531: positive regulation of tyrosine phosphorylation of STAT protein |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0042517: positive regulation of tyrosine phosphorylation of Stat3 protein |
ECO:0000314: |
P |
Figure 6 - shows CT1 positive regulation of STAT3 phosphorylation. |
complete | ||||
|
involved_in |
GO:0042531: positive regulation of tyrosine phosphorylation of STAT protein |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0016324: apical plasma membrane |
ECO:0000314: |
C |
Figure 5 - CNTFR normally in the apical membrane. |
complete | ||||
|
part_of |
GO:0016324: apical plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0016324: apical plasma membrane |
ECO:0000314: |
C |
Figure 5 - OsMRβ normally in the apical membrane |
complete | ||||
|
part_of |
GO:0016324: apical plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0016324: apical plasma membrane |
ECO:0000314: |
C |
Figure 5 - gp130 is normally found in apical membrane. |
complete | ||||
|
part_of |
GO:0016324: apical plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
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