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.
Keywords: Matrix metalloproteinases; Microglia; Podoplanin; Traumatic brain injury.
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