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Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury
Open accessAbstract
Growing evidence suggests that galectin-3 is involved in fine tuning of the inflammatory responses at the periphery, however, its role in injured brain is far less clear. Our previous work demonstrated upregulation and coexpression of galectin-3 and IGF-1 in a subset of activated/proliferating microglial cells after stroke. Here, we tested the hypothesis that galectin-3 plays a pivotal role in mediating injury-induced microglial activation and proliferation. By using a galectin-3 knock-out mouse ( Gal-3KO ), we demonstrated that targeted disruption of the galectin-3 gene significantly alters microglia activation and induces ∼4-fold decrease in microglia proliferation. Defective microglia activation/proliferation was further associated with significant increase in the size of ischemic lesion, ∼2-fold increase in the number of apoptotic neurons, and a marked deregulation of the IGF-1 levels. Next, our results revealed that contrary to WT cells, the Gal3-KO microglia failed to proliferate in response to IGF-1. Moreover, the IGF-1-mediated mitogenic microglia response was reduced by N -glycosylation inhibitor tunicamycine while coimmunoprecipitation experiments revealed galectin-3 binding to IGF-receptor 1 (R1), thus suggesting that interaction of galectin-3 with the N -linked glycans of receptors for growth factors is involved in IGF-R1 signaling. While the canonical IGF-1 signaling pathways were not affected, we observed an overexpression of IL-6 and SOCS3, suggesting an overactivation of JAK/STAT3, a shared signaling pathway for IGF-1/IL-6. Together, our findings suggest that galectin-3 is required for resident microglia activation and proliferation in response to ischemic injury.
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“Microglial proliferation has been shown to be the main contributor to increased microglial numbers under certain disease states such as ischemia, facial nerve transection, prion disease, and Alzheimer’s disease [42, 61–64].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [62]
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Metadata
- Authors
- Lalancette-Hébert, M., Swarup, V., Beaulieu, J. M., Bohacek, I., Abdelhamid, E., Weng, Y. C., Sato, S., & Kriz, J.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Université Laval (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-07-25
- Volume
- 32
- Issue
- 30
- Pages
- 10383-10395
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6703730
- OpenAlex
- W2140635355
- Cited by
- 251
- References
- 65
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 10 · 2023: 19 · 2022: 23 · 2021: 32 · 2020: 21 · 2019: 19 · 2018: 24 · 2017: 18 · 2016: 22 · 2015: 21 · 2014: 12 · 2013: 11 · 2012: 4
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- galectin-3, microglial activation, microglial proliferation, ischemic stroke, ischemic injury, insulin-like growth factor I, IGF-1 receptor, N-glycosylation, tunicamycin, JAK/STAT3 signaling, interleukin-6, SOCS3, neuronal apoptosis
- MeSH terms
- Animals, Brain, Cells, Cultured, Brain Ischemia, Insulin-Like Growth Factor I, Macrophages, Signal Transduction, Interleukin-6, Up-Regulation, Microglia, Mice, Knockout, Galectin 3, Cell Proliferation, STAT3 Transcription Factor, Mice
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