Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration
Open accessAbstract
Identifying the initiation signals for tissue regeneration in vertebrates is one of the major challenges in regenerative biology. Much of the research thus far has indicated that certain growth factors have key roles. Here we show that complement fragment C3a is sufficient to induce complete regeneration of the embryonic chick retina from stem/progenitor cells present in the eye, independent of fibroblast growth factor receptor signaling. Instead, C3a induces retina regeneration via STAT3 activation, which in turn activates the injury- and inflammation-responsive factors, IL-6, IL-8 and TNF-α. This activation sets forth regulation of Wnt2b, Six3 and Sox2, genes associated with retina stem and progenitor cells. Thus, our results establish a mechanism for retina regeneration based on injury and inflammation signals. Furthermore, our results indicate a unique function for complement anaphylatoxins that implicate these molecules in the induction and complete regeneration of the retina, opening new avenues of experimentation in the field. Components of the complement system have been shown to promote liver regeneration. Haynes et al. demonstrate that the complement fragment C3a can induce regeneration of the embryonic chick retina from stem and progenitor cells of the ciliary margin via activation of STAT3 and other downstream signalling pathways.
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Complement molecules C3a and C5a activate canonical JAK-STAT3 signaling via cytokine intermediates in models of retinal and liver regeneration.
“The complement molecules C3a and C5a have been shown to activate the canonical JAK-STAT3 signaling via cytokine intermediates in models of retinal and liver regeneration (Haynes et al., 2013; He et al., 2009; Strey et al., 2003).”
From Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer’s Disease (2018) · cites this paper as Haynes et al., 2013
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- Authors
- Haynes, T., Luz-Madrigal, A., Reis, E. S., Echeverri Ruiz, N. P., Grajales-Esquivel, E., Tzekou, A., Tsonis, P. A., Lambris, J. D., & Del Rio-Tsonis, K.
- Affiliations
- Miami University (US)
- University of Pennsylvania (US)
- University of Dayton (US)
- Venue
- Nature Communications
- Published
- 2013-08-14
- Volume
- 4
- Issue
- 1
- Pages
- 2312-2312
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3753547
- OpenAlex
- W2169720904
- Cited by
- 87
- References
- 57
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 5 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 10 · 2014: 13
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (0821211, AI068730)
- University of Miami
- University of Cincinnati
- Consejo Nacional de Ciencia y Tecnología (142523, 162930)
- National Eye Institute (EY020633, EY17319, EY-10540, R01EY020633, R01EY010540, R01EY017319)
- National Institute of Allergy and Infectious Diseases (AI 068730, P01AI068730)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- retinal regeneration, embryonic chick retina, ciliary margin, STAT3 signaling, interleukin-6, interleukin-8, TNF-α, WNT2B, Six3, SOX2, inflammation, tissue regeneration, complement system
- MeSH terms
- Homeobox Protein SIX3, Animals, Chick Embryo, Enzyme Activation, Eye Proteins, Nerve Tissue Proteins, Organ Culture Techniques, Regeneration, Retina, Tumor Necrosis Factor-alpha, Interleukin-6, Complement C3a, Interleukin-8, Homeodomain Proteins, MAP Kinase Signaling System, Tissue Engineering, Guided Tissue Regeneration, STAT3 Transcription Factor, SOXB1 Transcription Factors, Wnt3 Protein
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