Article
Biochemistry & Molecular Biology
Benjamin J. Buckley, Ashna Kumar, Ashraf Aboelela, Richard S. Bujaroski, Xiuju Li, Hiwa Majed, Larry Fliegel, Marie Ranson, Michael J. Kelso
Summary: The K+-sparing diuretic amiloride has demonstrated off-target anti-cancer effects by inhibiting the serine protease urokinase-type plasminogen activator (uPA) and the sodium-hydrogen exchanger isoform-1 (NHE1). Through screening, new chemotype-matched, non-cytotoxic probes have been identified as selective uPA inhibitors, dual-targeting inhibitors, and high-NHE1 potency inhibitors for dissecting the pharmacological effects of selective uPA and NHE1 inhibition versus dual-uPA/NHE1 inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiuju Li, Benjamin Buckley, Konstantin Stoletov, Yang Jing, Marie Ranson, John D. Lewis, Mike Kelso, Larry Fliegel
Summary: This study examined the role of NHE1 and uPA in prostate cancer cell migration and colony formation, finding that only uPA activity played a critical role in cell migration and colony formation, while the effect of NHE1 was minor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Urology & Nephrology
Victor M. Schuettfort, Benjamin Pradere, David D'Andrea, Nico C. Grossmann, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Pierre I. Karakiewicz, Reza Sari Motlagh, Satoshi Katayama, Yair Lotan, Douglas Scherr, Mohammad Abufaraj, Harun Fajkovica, Eva Comperat, Dmitry Enikeev, Shahrokh F. Shariat
Summary: Elevated preoperative plasma levels of uPA, SuPAR, and PAI-one were confirmed to be associated with aggressive disease features and worse survival outcomes in patients treated with RC for UCB. These biomarkers have the potential to identify patients who may benefit from intensified/multimodal therapy and improve the discriminatory power of predictive/prognostic models.
JOURNAL OF UROLOGY
(2021)
Article
Urology & Nephrology
Ruizhao Li, Zhiyong Xie, Li Zhang, Ying Huang, Jianchao Ma, Wei Dong, Zhilian Li, Yuanhan Chen, Huaban Liang, Yanhua Wu, Xingchen Zhao, Wenjian Wang, Zhiming Ye, Shuangxin Liu, Wei Shi, Xinling Liang
Summary: This study found that amiloride can significantly decrease urinary albumin creatinine ratio (uACR) in patients with DKD, and also reduce serum and urinary suPAR levels. Elevated levels of urinary suPAR were positively associated with uPCR and uACR, indicating its potential as a biomarker for DKD prognosis.
Review
Biochemistry & Molecular Biology
Manuel Yepes, Yena Woo, Cynthia Martin-Jimenez
Summary: The neurovascular unit is a complex structure involving various cells and components that are essential for maintaining normal neuronal function. Plasminogen activators play a crucial role in regulating the function of the neurovascular unit, with dysfunction leading to neurodegenerative disorders. Research on the expression and function of tissue-type plasminogen activator and urokinase-type plasminogen activator in the neurovascular unit has provided valuable insights into neurovascular and neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Koji Sugioka, Teruo Nishida, Aya Kodama-Takahashi, Junko Murakami, Fukutaro Mano, Kiyotaka Okada, Masahiko Fukuda, Shunji Kusaka
Summary: Corneal fibroblasts are regulated by collagen, and the targeting of Endo180 and uPA receptor may play a role in the regulation of alpha-SMA expression in a manner dependent on TGF-beta signaling. uPA deficiency may promote the interaction between collagen and Endo180 and increase alpha-SMA expression.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Julia Elrod, Annika Heuer, Jasmin Knopf, Janina Schoen, Lavinia Schoenfeld, Magdalena Trochimiuk, Carolin Stiel, Birgit Appl, Laia Pagerols Raluy, Ceren Saygi, Leticija Zlatar, Sami Hosari, Dmytro Royzman, Thomas H. Winkler, Guenter Lochnit, Moritz Leppkes, Robert Gruetzmann, Georg Schett, Christian Tomuschat, Konrad Reinshagen, Martin Herrmann, Tobias A. Fuchs, Michael Boettcher
Summary: Peritoneal adhesions, commonly occurring conditions causing intestinal obstruction and pelvic pain, are poorly understood. However, DNases have been found to significantly reduce the formation of adhesions in experimental models.
Article
Pharmacology & Pharmacy
Maria D. Valls, Maria Soldado, Jorge Arasa, Miguel Perez-Aso, Adrienne J. Williams, Bruce N. Cronstein, M. Antonia Noguera, M. Carmen Terencio, M. Carmen Montesinos
Summary: Activation of adenosine A(2A) receptor can promote angiogenesis by increasing the expression of annexin A2 in human dermal microvascular endothelial cells, which enhances fibrinolysis and contributes to wound healing and tissue revascularization.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chung-Ze Wu, Li-Chien Chang, Chao-Wen Cheng, Te-Chao Fang, Yuh-Feng Lin, Dee Pei, Jin-Shuen Chen
Summary: The study investigated the relationship between urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues using obese mouse models. Results showed that triglyceride levels, insulin resistance, and body weight increased with duration on a high fat diet (HFD), while the expression of uPA decreased in brown adipose tissue (BAT) in obese mice fed a HFD. These findings suggest a potential association between BAT fibrosis and dysfunction in obese models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Ashna A. Kumar, Benjamin J. Buckley, Marie Ranson
Summary: This review provides an overview of the role of the urokinase plasminogen activation system (uPAS) in pancreatic cancer, with a focus on pancreatic ductal adenocarcinoma (PDAC), and summarizes the substantial evidence supporting the role of uPAS components in this disease. The review further outlines the potential clinical utility of uPAS components as diagnostic and prognostic biomarkers for PDAC, as well as the rationale for developing novel uPAS-targeted therapeutics.
Article
Endocrinology & Metabolism
Ariel Diaz, Paola Merino, Patrick McCann, Manuel A. Yepes, Laura G. Quiceno, Enrique Torre, Amelia Tomkins, Xiaodong Zhang, Chadwick M. Hales, Frank C. Tong, Manuel Yepes
Summary: Studies show that uPA is preferentially found in specific cortical layers of the gyrencephalic cortex of non-human primates, and most uPA is associated with pre-synaptic vesicles in murine and human neurons. Cerebral ischemia reduces intact synaptic contacts, uPA and NCAD expression in surrounding tissue areas, while treatment with recombinant uPA can induce NCAD-mediated repair of synaptic contacts after ischemic onset.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Paola Manzo, Valentina Giudice, Filomena Napolitano, Danilo De Novellis, Bianca Serio, Paolo Moscato, Nunzia Montuori, Carmine Selleri
Summary: The microenvironment is crucial for multiple myeloma development and progression. Macrophages and the urokinase plasminogen activator receptor (uPAR) system play important roles in these processes. Inhibitors of uPAR have shown potential therapeutic effects in primary multiple myeloma cells, reducing interleukein-6 and DKK-1 levels in culture medium. However, further studies are needed to validate these preliminary results.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Torry A. Tucker, Steven Idell
Summary: This review discusses the fibrinolytic pathway, how local derangements of fibrinolysis promote extravascular fibrin deposition, and how pleural mesothelial cells contribute to lung scarring. It also explores the diagnostic value of soluble uPAR in grading pleural effusions, and the clinical importance of single-chain urokinase plasminogen activator (uPA) for treating loculated pleural collections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Obstetrics & Gynecology
Esra Demirel, Reem Sabouni, Neelima Chandra, Ov D. Slayden, David F. Archer
Summary: The study investigates the distribution and concentrations of several receptors and activators within the primate endometrium during artificial menstrual cycles, showing similarities in their expression patterns suggesting overlapping pathways. These findings indicate potential interactions between the plasminogen activator system and steroid receptors in the endometrium.
REPRODUCTIVE SCIENCES
(2022)
Review
Cell Biology
Steven L. Gonias
Summary: Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteases that play a crucial role in fibrinolysis in mammalian systems. Cells have evolved receptor systems to detect and respond to tPA and uPA, impacting various aspects of cell physiology. This review highlights the structure and function of plasminogen activator receptor assemblies and their role in regulating innate immunity and inflammation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)