The tripartite complex formed by the urokinase receptor, urokinase, and its inhibitor is an enzymatic system that controls plasmin formation involved in degradation of extracellular matrix proteins. With the use of magnetic twisting cytometry with urokinase-coated ferromagnetic beads, we applied mechanical stress directly to the urokinase receptor on the surface of human myogenic cells in culture. The stiffness and the stiffening response measured through the urokinase receptor resembled those of integrins, which are linked mechanically to the cytoskeleton. Furthermore, stiffness decreased with disruption of actin microfilaments. These results demonstrate that the urokinase receptor is coupled mechanically to the cytoskeleton. Inhibition of the tripartite complex formation with antibodies led to a twofold increase in cytoskeletal stiffness. A stiffened cytoskeleton might impede cytoskeletal remodeling and reorganization and thus impede cell motility. Our results demonstrate that the urokinase receptor mediates mechanical force transfer across the cell surface. As such, it is a novel pathway to regulate cytoskeletal stiffness and, thereby, possibly to modulate motility of normal and abnormal adherent cells.
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http://dx.doi.org/10.1152/ajpcell.1995.268.4.C1062 | DOI Listing |
Sci Adv
January 2025
The Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).
View Article and Find Full Text PDFTransl Androl Urol
December 2024
Department of Urology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: Some studies suggest a potential association between plasma lipidome and erectile dysfunction (ED), but the underlying mechanism and whether circulating inflammatory proteins act as mediators remain unclear. The purpose of this study was to investigate the potential causal relationships between plasma lipidome, inflammatory proteins, and ED.
Methods: Plasma lipidome, circulating inflammatory proteins, and ED cases were identified based on the summary data from several large-scale genome-wide association studies (GWAS).
Prog Neuropsychopharmacol Biol Psychiatry
January 2025
Department of Psychiatry, University Medical Center Groningen, Groningen, the Netherlands.
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Introduction: We investigated the specific factors driving abnormal angiogenesis in Alzheimer's disease (AD) and its role in cerebrovascular lesions and neurodegeneration.
Methods: We assessed cerebrovascular pathologies, amyloid-beta (Aβ), and tau pathologies in post mortem human brains and detected 12 angiogenic factors in cerebrospinal fluid (CSF) from the China Aging and Neurodegenerative Disease Initiative (CANDI) cohort.
Results: We observed severe blood-brain barrier damage and elevated levels of the vascular marker CD31 in human AD brains, which had a stronger correlation with tau pathology than Aβ pathology.
Unlabelled: Chronic back pain (CBP) is the leading cause of disability affecting 1 in 10 people worldwide. Symptoms are marked by persistent lower back pain, reduced mobility, and heightened cold sensitivity. Here, we utilize a mouse model of CBP induced by injecting urokinase-type plasminogen activator (uPA), a proinflammatory agent in the fibrinolytic pathway, between the L2/L3 lumbar vertebrae.
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