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Updated: Jan 1, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Podoplanin influences the inflammatory phenotypes and mobility of microglia in traumatic brain injury
Maoxing Fei1, Handong Wang2, Mengliang Zhou3
1Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, PR China.
Abstract:
Traumatic brain injury (TBI) represents a major cause of death and disability worldwide. Exacerbated neuroinflammation following TBI causes secondary injury. Podoplanin (PDPN) is a small transmembrane mucin-like glycoprotein that promotes the inflammatory response in different tissues and cells. However, the contribution of PDPN to neuroinflammation and microglial activation is unknown. Here, we found that PDPN was correlated with microglial activation after TBI in mice. Meanwhile, PDPN expression could be induced by trauma-related stimuli, such as lipopolysaccharide (LPS), ATP, H2O2 and hemoglobin (Hb), in primary microglia. Furthermore, with Hb treatment in vitro, knockdown of PDPN could decrease the proportion of M1-like microglia and increase the proportion of M2-like microglia via reduced secretion of IL-1β and TNF-α and increased secretion of IL-10 and TGF-β compared to the control microglia. Immunofluorescence also showed that CD86-positive microglia were decreased and CD206-positive microglia were elevated in the PDPN-KD group. Additionally, PDPN knockdown impaired microglial mobility and phagocytosis and decreased the expression of matrix metalloproteinases (mainly MMP2 and MMP9). In summary, PDPN plays an important role in microglia-mediated inflammation and may serve as a potential target for TBI treatment.
Insights
Podoplanin (PDPN) exacerbates neuroinflammation after traumatic brain injury (TBI) by activating microglia. Reducing PDPN lessens inflammation and may offer a new therapeutic target for TBI.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Traumatic brain injury (TBI) is a leading cause of death and disability globally.
- Neuroinflammation following TBI contributes significantly to secondary injury.
- Podoplanin (PDPN) is implicated in inflammatory responses, but its role in TBI-induced neuroinflammation is unclear.
Purpose of the Study:
- To investigate the role of PDPN in microglial activation and neuroinflammation after TBI.
- To determine if PDPN influences microglial polarization and function in response to trauma-related stimuli.
Main Methods:
- Correlation analysis of PDPN expression and microglial activation in a mouse TBI model.
- In vitro studies exposing primary microglia to trauma-related stimuli (LPS, ATP, H2O2, Hb).
- Assessment of PDPN knockdown effects on microglial polarization (M1/M2 markers), cytokine secretion, mobility, phagocytosis, and matrix metalloproteinase (MMP) expression.
Main Results:
- PDPN expression correlated with microglial activation post-TBI.
- Trauma-related stimuli induced PDPN expression in primary microglia.
- PDPN knockdown shifted microglia from M1 to M2 phenotype, altering cytokine profiles (reduced IL-1β, TNF-α; increased IL-10, TGF-β).
- PDPN knockdown decreased microglial mobility and phagocytosis, and reduced MMP2/MMP9 expression.
Conclusions:
- PDPN plays a significant role in microglia-mediated inflammation following TBI.
- Targeting PDPN may represent a novel therapeutic strategy for mitigating TBI-induced neuroinflammation and secondary injury.
