The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and collagen V on the cell surface. We have determined the sites of expression of this novel receptor during murine postimplantation development. uPARAP/Endo180 was expressed in all tissues undergoing primary ossification, including the developing bones of the viscerocranium and calvarium that ossify intramembranously, and developing long bones undergoing endochondral ossification. uPARAP/Endo180 mRNA was expressed by both immature osteoblasts and by mature osteocalcin-producing osteoblasts-osteocytes, and was coexpressed with MMP-13. Interestingly, osteoblasts also expressed uPAR. Besides bone-forming tissues, uPARAP/Endo180 expression was detected only in a mesenchymal condensation of the midbrain and in the developing lungs. The data suggest a function of this novel protease receptor in bone development, possibly mediated through its interactions with uPAR, MMP-13, or collagen V.
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http://dx.doi.org/10.1038/labinvest.3780354 | DOI Listing |
Mol Ther
January 2025
Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia. Electronic address:
Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.
View Article and Find Full Text PDFiScience
January 2025
Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer-associated fibroblasts (CAFs) represent a major contributor to tumor growth. Cellular senescence is a state of cell-cycle arrest characterized by a pro-inflammatory phenotype. The potential impact of CAF senescence on tumor progression and the tumor microenvironment (TME) remains to be elucidated.
View Article and Find Full Text PDFAnim Behav
January 2025
Department of Anthropology, New York University, New York, NY, U.S.A.
The effect of the social environment on the proinflammatory immune response may mediate the relationship between social environment and fitness but remains understudied outside captive animals and human populations. Age can also influence both immune function and social behaviour, and hence may modulate their relationships. This study investigates the role of social interactions in driving the concentrations of two urinary markers of proinflammatory immune activation, neopterin and soluble urokinase plasminogen activator receptor (suPAR), in a free-ranging population of rhesus macaques, .
View Article and Find Full Text PDFRespir Res
January 2025
Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Background: Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29% of the cohort, which suggests pleural infection as the predominant etiology of pleural effusion in China. Medical thoracoscopy (MT) combined with intrapleural injection of Urokinase holds significant therapeutic value for patients with early to moderate-stage empyema. However, there remains a lack of high-quality evidence regarding the efficacy and safety of combining MT with intrapleural injection of Urokinase administration in patients with pleural infections.
View Article and Find Full Text PDFSci 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).
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