TNFα activates MAPK and Jak-Stat pathways to promote mouse Müller cell proliferation.
Open accessAbstract
Mouse Müller cells, considered as dormant retinal progenitors, often respond to retinal injury by undergoing reactive gliosis rather than displaying neural regenerative responses. Tumor necrosis factor alpha (TNFα) is a key cytokines induced after injury and implicated in mediating inflammatory and neural regenerative responses in zebrafish. To investigate the involvement of TNFα in mouse retinal injury, adult C57BL/6J mice were subjected to light damage for 14 consecutive days. TNFα was elevated in the retina of mice exposed to light damage, which induced Müller cell proliferation in vitro. Affymetrix microarray showed that, in Müller cells, TNFα induces up-regulation of inflammatory and proliferation-related genes, including NFKB2, leukemia inhibitory factor, interleukin-6, janus kinase (Jak) 1, Jak2, signal transducer and activator of transcription (Stat) 1, Stat2, mitogen-activated protein kinase (MAPK) 7, and MAP4K4 but down-regulation of neuroprogenitor genes, including Sox9, Ascl1, Wnt2 and Hes1. Blocking the Jak/Stat and MAPK pathways attenuated TNFα-induced Müller cell proliferation. These results suggest that TNFα may drive the proliferation and inflammatory response, rather than the neural regenerative potential, of mouse Müller cells.
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TNF-α activates the JAK/STAT signal pathway via the protein-gp130 on the cell membrane's surface, and so contributes to the control of central nervous system degenerative alterations.
“Numerous studies have revealed that TNF-α activates JAK/STAT signal pathway via the protein-gp130 on the cell membrane’s surface, and so contributes to the control of central nervous system degenerative alterations [63].”
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- Authors
- Niu, L., Fang, Y., Yao, X., Zhang, Y., Wu, J., Chen, D. F., & Sun, X.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Chen, Dong Feng
- Sun, Xinghuai
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 202
- Pages
- 108353
- ISSN
- 0014-4835 (ISSN-L)
- OpenAlex
- W3102008695
- Cited by
- 32
- References
- 40
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 13 · 2023: 6 · 2022: 5
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Experimental Eye Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- International Science and Technology Cooperation Programme (2015DFA31340)
- National Natural Science Foundation of China (NSFC81100667, 81020108017, 81430007)
- National Health and Family Planning Commission of the People's Republic of China (201302015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- TNF-α, Müller cells, retinal damage, light-induced retinal damage, reactive gliosis, cell proliferation, MAPK signaling, JAK/STAT signaling, neuroinflammation, retinal regeneration, SOX9, ASCL1, Wnt2, Hes1, MAP4K4, NFKB2, interleukin-6, leukemia inhibitory factor
- MeSH terms
- Animals, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Mice, Inbred C57BL, RNA, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Mitogen-Activated Protein Kinases, Models, Animal, Cell Proliferation, Mice, Ependymoglial Cells
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