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
Biophysics
Giulia Moro, Patrick Severin Sfragano, Jessica Ghirardo, Ylenia Mazzocato, Alessandro Angelini, Ilaria Palchetti, Federico Polo
Summary: The use of synthetic bioreceptors in biosensing platforms is gaining popularity. This case study compared the performance of two bicyclic peptides with different affinities for the human biomarker urokinase-type plasminogen activator (h-uPA). The study demonstrated the potential of synthetic bicyclic peptides and how receptor affinity can affect the performance of biosensing platforms.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Oncology
C. F. Singer, S. W. Jahn, M. Rudas, Z. Bago-Horvath, F. Fitzal, L. Abete, F. Moinfar, M. Gnant, M. Filipits
Summary: This study validates the prognostic role of urokinase-type plasminogen-activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) protein expression in archived tumor samples. The results show that stromal uPA expression is significantly associated with shorter distant recurrence-free survival in breast cancer. This study provides clinical evidence for the prognostic role of stromal uPA in women with hormone receptor-positive, early breast cancer.
Article
Biochemistry & Molecular Biology
Chen-Lin Yu, Meng-Shih Weng, Wei-Cheng Chen, Kai-Ting Chien, Chih-Wen Chi, Ching-Hu Chung, Chia-Wen Huang, Po-Chuan Wang, Chien-Chih Chen, An-Chi Tsai, Shih-Chia Liu, Shih-Wei Wang
Summary: Moscatilin inhibits the metastatic behavior of HCC cells without cytotoxicity, potentially through the Akt/NF-kappa B signaling pathway to impede HCC invasion and uPA expression. It may serve as a potential anti-metastatic agent against human HCC progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Yuki Matsui, Ken Kadoya, Yusuke Nagano, Takeshi Endo, Masato Hara, Gen Matsumae, Tomoaki Suzuki, Yasuhiro Yamamoto, Mohamad Alaa Terkawi, Norimasa Iwasaki
Summary: This study demonstrates that IL4 stimulated M2 macrophages can directly stimulate axon growth and enhance axon regeneration. The central axis underlying this effect is uPA-uPAR signaling pathway. These findings provide a potential novel therapy for peripheral nerve injury (PNI).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Ran Zhu, Ting-Wei Liu, Fan Liu
Summary: The study shows that treatment of acute pulmonary embolism (APE) with serine protease urokinase or urokinase-type plasminogen activator (uPA) can increase endogenous expression of uPA and its receptor uPAR. Using an in vitro hypoxia/reoxygenation model, the study reveals that hypoxia/reoxygenation induces cell apoptosis and secretion of certain molecules, which can be attenuated with exogenous uPA treatment. Additionally, hypoxia/reoxygenation leads to degradation of uPAR, but this degradation can be reversed with uPA treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Obstetrics & Gynecology
Yukiko Asano, Takayuki Iwaki, Kazuo Umemura, Naohiro Kanayama, Hiroaki Itoh
Summary: The study showed that fibrin had no effect on mouse blastocysts, but significantly suppressed trophoblast growth in human blastocysts. However, trophoblasts in human blastocysts then switched to growth promotion through increased fibrinolysis with urokinase-type plasminogen activator (uPA) activity.
HUMAN REPRODUCTION
(2021)
Article
Biophysics
Giulia Moro, Patrick Severin Sfragano, Jessica Ghirardo, Ylenia Mazzocato, Alessandro Angelini, Ilaria Palchetti, Federico Polo
Summary: The trend of using synthetic bioreceptors to develop biosensing platforms is gaining momentum. This case study compares the performance of a biosensing platform for the human biomarker h-uPA using two bicyclic peptides with different affinities for the target protein, showing the potential of synthetic bicyclic peptides applicability and the influence of bioreceptor affinity on the performance of the final sensing platform.
BIOSENSORS & BIOELECTRONICS
(2022)
Review
Cell Biology
Manuel Yepes
Summary: The repair of injured tissue involves complex processes such as cell proliferation, differentiation, and migration. Experimental evidence suggests that urokinase-type plasminogen activator (uPA) promotes cell migration by binding to its receptor (uPAR) on the cell surface. Neuronal cadherin and glycogen synthase kinase 3 beta also play important roles in this process.
NEURAL REGENERATION RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Asmaa Anwar Ismail, Baraah Tariq Shaker, Khalid Bajou
Summary: Angiogenesis is a process involving the migration and proliferation of endothelial cells to form new blood vessels. The plasminogen activator-plasmin system plays a major role in this process, but paradoxically, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor promote angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
Cardiac & Cardiovascular Systems
Sultan Tousif, Anand P. P. Singh, Prachi Umbarkar, Cristi Galindo, Nicholas Wheeler, Angelica Toro Cora, Qinkun Zhang, Sumanth D. D. Prabhu, Hind Lal
Summary: The tyrosine kinase inhibitor ponatinib is found to be the most cardiotoxic agent among all approved tyrosine kinase inhibitors. Through the use of various models, the study reveals that ponatinib induces cardiac inflammation and dysfunction through the activation of the S100A8/A9-TLR4-NLRP3-IL-1beta signaling pathway. These findings provide important preclinical data and rationale for managing ponatinib-induced cardiotoxicity.
CIRCULATION RESEARCH
(2023)
Article
Hematology
Bradley K. Wacker, Nagadhara Dronadula, Jingwan Zhang, David A. Dichek
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2017)
Letter
Multidisciplinary Sciences
Isaac Emery
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Bradley K. Wacker, Lianxiang Bi, David A. Dichek
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2018)
Article
Hematology
Bradley K. Wacker, Nagadhara Dronadula, Lianxiang Bi, Alexis Stamatikos, David A. Dichek
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2018)
Article
Biotechnology & Applied Microbiology
Alexis Stamatikos, Nagadhara Dronadula, Philip Ng, Donna Palmer, Ethan Knight, Bradley K. Wacker, Chongren Tang, Francis Kim, David A. Dichek
HUMAN GENE THERAPY
(2019)
Article
Multidisciplinary Sciences
Lianxiang Bi, Bradley K. Wacker, David A. Dichek
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2018)
Article
Biotechnology & Applied Microbiology
Alexis Stamatikos, Ethan Knight, Lucia Vojtech, Lianxiang Bi, Bradley K. Wacker, Chongren Tang, David A. Dichek
HUMAN GENE THERAPY
(2020)
Article
Cardiac & Cardiovascular Systems
Tomas Vaisar, Jie H. Hu, Nathan Airhart, Kate Fox, Jay Heinecke, Roberto F. Nicosia, Ted Kohler, Zachary E. Potter, Gabriel M. Simon, Melissa M. Dix, Benjamin F. Cravatt, Sina A. Gharib, David A. Dichek
CIRCULATION RESEARCH
(2020)
Article
Hematology
Lianxiang Bi, Bradley K. Wacker, Alexis Stamatikos, Meena Sethuraman, Kaushik Komandur, David A. Dichek
Summary: Injection of high-titer lentiviral vectors via the jugular vein transduces cells in the spleen and liver but does not efficiently transduce the aorta.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Hematology
Jay Zhu, Stoyan Angelov, Ilkay Alp Yildirim, Hao Wei, Jie Hong Hu, Mark W. Majesky, Frank Brozovich, Francis Kim, David A. Dichek
Summary: Loss-of-function variants in the TGF-beta signaling pathway can lead to endothelial dysfunction and aortic hypercontractility, potentially contributing to the development of aortic aneurysms.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Letter
Hematology
David A. Dichek
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Goren Saenz-Pipaon, David A. Dichek
Summary: Discovered three decades ago, microRNAs (miRNAs) are now recognized as key players in the pathophysiology of multiple human diseases, including those affecting the cardiovascular system. As such, miRNAs have emerged as promising therapeutic targets for preventing the onset and/or progression of several cardiovascular diseases. The use of antagomirs, such as anti-miRNA antisense oligonucleotides, shows potential in precisely blocking specific miRNAs and treating major cardiovascular diseases. Recent advancements in antisense oligonucleotide chemistry and targeted delivery systems have improved efficacy and safety, providing hope for future clinical applications.
Article
Biochemistry & Molecular Biology
Bradley K. Wacker, Lianxiang Bi, Li Liu, Mary G. Sorci-Thomas, Philip Ng, Donna J. Palmer, Chongren Tang, David A. Dichek
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2023)
Article
Medicine, Research & Experimental
Lianxiang Bi, Bradley K. Wacker, Kaushik Komandur, Nicole Sanford, David A. Dichek
Summary: This study successfully reduced lipid and macrophage accumulation in vein grafts by transducing them with Apolipoprotein AI using gene therapy. This method shows promise in preventing vein-graft failure caused by atherosclerosis.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Medicine, Research & Experimental
Nathalie Pamir, Patrick M. Hutchins, Graziella E. Ronsein, Hao Wei, Chongren Tang, Riku Das, Tomas Vaisar, Edward Plow, Volker Schuster, Catherine A. Reardon, Richard Weinberg, David A. Dichek, Santica Marcovina, Godfrey S. Getz, Jay W. Heinecke