Article ; Online: Role of Formyl Peptide Receptors and β-Arrestin-1 in suPAR Signal Transduction in Mouse Podocytes: Interactions with αVβ3-Integrin.
2024 Volume 13, Issue 2
Abstract: The 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- ... ...
| Abstract | The 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. |
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| MeSH term(s) | Animals ; Mice ; beta-Arrestin 1 ; Integrin beta3 ; Podocytes ; Reactive Oxygen Species ; Receptor for Advanced Glycation End Products ; Receptors, Formyl Peptide ; Receptors, Urokinase Plasminogen Activator ; Signal Transduction ; Integrin alpha5 |
| Chemical Substances | beta-Arrestin 1 ; Integrin beta3 ; Reactive Oxygen Species ; Receptor for Advanced Glycation End Products ; Receptors, Formyl Peptide ; Receptors, Urokinase Plasminogen Activator ; Integrin alpha5 |
| Language | English |
| Publishing date | 2024-01-17 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2661518-6 |
| ISSN | 2073-4409 ; 2073-4409 |
| ISSN (online) | 2073-4409 |
| ISSN | 2073-4409 |
| DOI | 10.3390/cells13020172 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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