Cited by 251Neuroinflammation and Neurodegeneration MechanismsGalectins and Cancer BiologyNeurogenesis and neuroplasticity mechanisms

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

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Lalancette-Hébert, Mélanie, Swarup, Vivek, Beaulieu, Jean Martin, Bohacek, Ivan, Abdelhamid, Essam, Weng, Yuan Cheng, Sato, Sachiko, Kriz, Jasna·2012·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.1498-12.2012

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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].”

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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
Published
2012-07-25
Volume
32
Issue
30
Pages
10383-10395
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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