Podoplanin drives motility of active macrophage via regulating Filamin C during helicobacter pylori infection
Document Type
Article
Publication Date
10-11-2021
Abstract
Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1 beta production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.
Keywords
Podoplanin, Macrophage, Helicobacter pylori, Cell migration, Filamin C, Interleukin-1 beta
Divisions
fac_med
Funders
Ministry of Education, Malaysia[FP133-2019A],Institut Merieux, France[IF039-2017],Malaysia Public Service Department (JPA)
Publication Title
Frontiers in Immunology
Volume
12
Publisher
Frontiers Media
Publisher Location
AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND