| Autor: |
Kim EY; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA., Dryer SE; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.; Department of Biomedical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, TX 77204, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Cells [Cells] 2024 Jan 17; Vol. 13 (2). Date of Electronic Publication: 2024 Jan 17. |
| DOI: |
10.3390/cells13020172 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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