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Updated: Jul 4, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Lamin A/C mediates microglial activation by modulating cell proliferation and immune response
Haotian Liu1,2, Xinnan Liu2, Shiqi Luo2
1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, China.
Abstract:
Lamin A/C is involved in macrophage activation and premature aging, also known as progeria. As the resident macrophage in brain, overactivation of microglia causes brain inflammation, promoting aging and brain disease. In this study, we investigated the role of Lamin A/C in microglial activation and its impact on progeria using Lmna-/- mice, primary microglia, Lmna knockout (Lmna-KO) and Lmna-knockdown (Lmna-KD) BV2 cell lines. We found that the microglial activation signatures, including cell proliferation, morphology changes, and proinflammatory cytokine secretion (IL-1β, IL-6, and TNF-α), were significantly suppressed in all Lamin A/C-deficient models when stimulated with LPS. TMT-based quantitative proteomic and bioinformatic analysis were further applied to explore the mechanism of Lamin A/C-regulated microglia activation from the proteome level. The results revealed that immune response and phagocytosis were impaired in Lmna-/- microglia. Stat1 was identified as the hub protein in the mechanism by which Lamin A/C regulates microglial activation. Additionally, DNA replication, chromatin organization, and mRNA processing were also altered by Lamin A/C, with Ki67 fulfilling the main hub function. Lamin A/C is a mechanosensitive protein and, the immune- and proliferation-related biological processes are also regulated by mechanotransduction. We speculate that Lamin A/C-mediated mechanotransduction is required for microglial activation. Our study proposes a novel mechanism for microglial activation mediated by Lamin A/C.
Insights
Lamin A/C deficiency suppresses microglial activation, impacting immune response and cell proliferation. This finding reveals a novel role for Lamin A/C in regulating brain inflammation and aging processes.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Lamin A/C influences macrophage activation and premature aging (progeria).
- Microglial overactivation in the brain causes inflammation, accelerating aging and neurodegenerative diseases.
Purpose of the Study:
- To investigate Lamin A/C's role in microglial activation and its link to progeria.
- To elucidate the molecular mechanisms underlying Lamin A/C-mediated microglial regulation.
Main Methods:
- Utilized Lamin A/C-deficient mice (Lmna-/-), primary microglia, and Lmna knockout/knockdown BV2 cell lines.
- Stimulated microglia with lipopolysaccharide (LPS) to assess activation.
- Employed TMT-based quantitative proteomics and bioinformatics for proteome-level analysis.
Main Results:
- Lamin A/C deficiency significantly suppressed microglial activation markers (proliferation, morphology, cytokine secretion).
- Immune response and phagocytosis were impaired in Lamin A/C-deficient microglia.
- Identified Stat1 and Ki67 as key regulatory proteins in Lamin A/C-mediated microglial function and proliferation.
Conclusions:
- Lamin A/C is crucial for normal microglial activation, immune response, and proliferation.
- Lamin A/C-mediated mechanotransduction may be essential for microglial activation.
- This study proposes a novel mechanism for microglial activation involving Lamin A/C.
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