Role of Formyl Peptide Receptors and β-Arrestin-1 in suPAR Signal Transduction in Mouse Podocytes: Interactions with αVβ3-Integrin

dc.contributor.authorKim, Eun Young
dc.contributor.authorDryer, Stuart E.
dc.date.accessioned2024-01-26T14:10:45Z
dc.date.available2024-01-26T14:10:45Z
dc.date.issued2024-01-17
dc.date.updated2024-01-26T14:10:45Z
dc.description.abstractThe soluble urokinase plasminogen activator receptor (suPAR) has been implicated in a wide range of pathological conditions including primary nephrotic syndromes and acute kidney injuries. suPAR can trigger transduction cascades in podocytes by outside-in activation of αVβ3-integrin, but there is evidence that the functional cell surface response element is actually a complex of different types of receptors, which may also include the receptor for advanced glycation end-products (RAGE) and formyl peptide receptors (FPRs). Here we observed that ROS accumulation and Src activation could be evoked by continuous 24 h exposure to either suPAR or the FPR agonist fMLF. Responses to suPAR and fMLF were completely blocked by either the FPR antagonist WRW4 or by the αV-integrin inhibitor cilengitide. Moreover, endogenous podocyte mouse Fpr1 co-immunoprecipitates with β3-integrin, suggesting that these receptors occur as a complex on the cell surface. suPAR- and fMLF-evoked activation of Src and ROS differed in time course. Thus, robust pertussis toxin (PTX)-sensitive responses were evoked by 60 min exposures to fMLF but not to suPAR. By contrast, responses to 24 h exposures to either suPAR or fMLF were PTX-resistant and were instead abolished by knockdown of β-arrestin-1 (BAR1). FPRs, integrins, and RAGE (along with various Toll-like receptors) can all function as pattern-recognition receptors that respond to “danger signals” associated with infections and tissue injury. The fact that podocytes express such a wide array of pattern-recognition receptors suggests that the glomerular filter is designed to change its function under certain conditions, possibly to facilitate clearance of toxic macromolecules.
dc.identifierdoi: 10.3390/cells13020172
dc.identifier.citationCells 13 (2): 172 (2024)
dc.identifier.urihttps://hdl.handle.net/10657/16172
dc.titleRole of Formyl Peptide Receptors and β-Arrestin-1 in suPAR Signal Transduction in Mouse Podocytes: Interactions with αVβ3-Integrin

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