Podoplanin drives motility of active macrophage via regulating Filamin C during helicobacter pylori infection

Cheok, Yi Ying and Tan, Grace Min Yi and Fernandez, Keith Conrad and Chan, Yee Teng and Lee, Chalystha Yie Qin and Cheong, Heng Choon and Looi, Chung Yeng and Vadivelu, Jamunarani S. and Abdullah, Suhailah and Wong, Won Fen (2021) Podoplanin drives motility of active macrophage via regulating Filamin C during helicobacter pylori infection. Frontiers in Immunology, 12. ISSN 1664-3224, DOI https://doi.org/10.3389/fimmu.2021.702156.

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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.</p>

Item Type: Article
Funders: Ministry of Education, Malaysia[FP133-2019A], Institut Merieux, France[IF039-2017], Malaysia Public Service Department (JPA)
Uncontrolled Keywords: Podoplanin;Macrophage;Helicobacter pylori;Cell migration; Filamin C;Interleukin-1 beta
Subjects: Q Science > QR Microbiology
R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 12 Sep 2022 04:44
Last Modified: 12 Sep 2022 04:44
URI: http://eprints.um.edu.my/id/eprint/34334

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