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 is the main contributor to increased microglial numbers under certain disease states such as ischemia, facial nerve transection, prion disease, and Alzheimer's disease.
“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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- 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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