Article
Biochemistry & Molecular Biology
Roberta Lugano, Kalyani Vemuri, Stefano Barbera, Maurizio Orlandini, Elisabetta Dejana, Lena Claesson-Welsh, Anna Dimberg
Summary: CD93 regulates the stability of VE-cadherin at endothelial junctions by interacting with VE-cadherin and limiting its phosphorylation and turnover. CD93 deficiency leads to increased phosphorylation of VE-cadherin, displacing it from endothelial cell-cell contacts and disrupting endothelial junctions, resulting in enhanced blood-brain barrier permeability. This mechanism is regulated through the Rho/Rho kinase-dependent pathway.
Article
Biochemistry & Molecular Biology
Typhaine Anquetil, Romain Solinhac, Aude Jaffre, Gaetan Chicanne, Julien Viaud, Jean Darcourt, Cyrille Orset, Eva Geuss, Christoph Kleinschnitz, Bart Vanhaesebroeck, Denis Vivien, Karim Hnia, Vincent Larrue, Bernard Payrastre, Marie-Pierre Gratacap
Summary: Protecting endothelial cells is critical in preventing the impact of vascular leakage and edema on pathological conditions. PI3KC2 beta could be a potential new therapeutic target for treating aggravating lesions following ischemic stroke.
Article
Pharmacology & Pharmacy
Daniel Rand, Orly Ravid, Dana Atrakchi, Hila Israelov, Yael Bresler, Chen Shemesh, Liora Omesi, Sigal Liraz-Zaltsman, Fabien Gosselet, Taber S. Maskrey, Michal Schnaider Beeri, Peter Wipf, Itzik Cooper
Summary: This study aimed to investigate the molecular response to blood-brain barrier (BBB) damage and to identify potential therapeutic approaches to protect the BBB integrity. The research found that iron chelators and a novel nitroxide can decrease cell death induced by injury and rescue BBB functionality, highlighting a potential treatment strategy for neurological diseases with compromised BBB integrity.
Article
Biochemistry & Molecular Biology
Nida Arif, Maren Zinnhardt, Alengo Nyamay'Antu, Denise Teber, Randy Brueckner, Kerstin Schaefer, Yu-Tung Li, Britta Trappmann, Carsten Grashoff, Dietmar Vestweber
Summary: The study reveals the mechanism of leukocyte extravasation during the immune response, which involves the destabilization of endothelial junctions through PECAM-1-SHP2-triggered dephosphorylation of VE-cadherin-Y731. This process requires various biochemical and biomechanical factors, such as Ca2+ signaling, non-muscle myosin II activation, and endothelial cell tension.
Article
Medicine, Research & Experimental
Xuechao Jiang, Tingting Li, Bojian Li, Wei Wei, Fen Li, Sun Chen, Rang Xu, Kun Sun
Summary: SOX7 inhibits EndMT during OFT development by up-regulating the endothelial-specific adhesion molecule VE-cadherin. Mutations in SOX7 can lead to impaired EndMT by regulating VE-cadherin, potentially contributing to the molecular mechanisms associated with SOX7 in CTD pathogenesis.
Article
Multidisciplinary Sciences
Rina Hashimoto, Junya Takahashi, Keisuke Shirakura, Risa Funatsu, Kaori Kosugi, Sayaka Deguchi, Masaki Yamamoto, Yugo Tsunoda, Maaya Morita, Kosuke Muraoka, Masato Tanaka, Tomoaki Kanbara, Shota Tanaka, Shigeyuki Tamiya, Nagisa Tokunoh, Atsushi Kawai, Masahito Ikawa, Chikako Ono, Keisuke Tachibana, Masuo Kondoh, Masanori Obana, Yoshiharu Matsuura, Akihiro Ohsumi, Takeshi Noda, Takuya Yamamoto, Yasuo Yoshioka, Yu-Suke Torisawa, Hiroshi Date, Yasushi Fujio, Miki Nagao, Kazuo Takayama, Yoshiaki Okada
Summary: This study found that SARS-CoV-2 decreases the expression of Claudin-5 (CLDN5), a tight junction protein, and disrupts vascular endothelial cadherin-mediated adherens junctions, thereby leading to the disruption of the endothelial barrier in respiratory organs. The down-regulation of CLDN5 expression was observed in the lungs of a COVID-19 patient. The overexpression of CLDN5 or treatment with Fluvastatin rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. Inducing CLDN5 expression is identified as a therapeutic strategy against COVID-19.
Review
Physiology
Weijin Nan, Yuxi He, Shurong Wang, Yan Zhang
Summary: VE-cadherin is an endothelium-specific adhesion protein found in the junctions between endothelial cells. It is crucial for maintaining the homogeneity of endothelial cells and plays important roles in vascular development, permeability, and tumor angiogenesis.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Medicine, General & Internal
Shiyue Wang, Xin Li, Han Jiang, Jian Zhang
Summary: In this study, the diagnostic value of serum VEC and Vcn for TBAD was evaluated. The results showed that the concentrations of VEC and Vcn were significantly higher in TBAD patients compared to healthy controls. Combined detection of VEC and Vcn improved the accuracy of TBAD diagnosis. High serum Vcn concentration was associated with increased risk of visceral malperfusion in TBAD patients. Therefore, VEC and Vcn have the potential to be serum markers for TBAD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Peripheral Vascular Disease
Joana Amado-Azevedo, Anne-Marieke D. van Stalborch, Erik T. Valent, Kalim Nawaz, Jan van Bezu, Etto C. Eringa, Femke P. M. Hoevenaars, Iris M. De Cuyper, Peter L. Hordijk, Victor W. M. van Hinsbergh, Geerten P. van Nieuw Amerongen, Jurjan Aman, Coert Margadant
Summary: The kinase Arg/Abl2 has been identified as a mediator of endothelial barrier disruption. Depletion of Arg in endothelial cells resulted in activation of RhoA and Rac1, increased cell spreading and elongation, and redistribution of integrin-dependent cell-matrix adhesions. In vivo, genetic deletion of Arg diminished vascular leak in the skin and lungs, suggesting therapeutic inhibition of Arg may be a feasible strategy for treating conditions characterized by vascular leak.
Article
Biology
Boyang Ren, Huan Xia, Yijun Liao, Hang Zhou, Zhongnan Wang, Yaoyao Shi, Mingzhao Zhu, Juan Carlos Zuniga-Pfluecker
Summary: This study reveals a novel role of endothelial SIRP alpha signaling for thymic HPC homing for T cell development.
Article
Biochemistry & Molecular Biology
Nikolaos P. E. Kadoglou, Marianna Stasinopoulou, Eirini Christodoulou, Georgia Valsami, Nikolaos Kostomitsopoulos
Summary: This study evaluated the effects of exercise training on the progression of atherosclerotic lesions in hypercholesterolemic mice. It was found that exercise training reduced aortic stenosis, increased fibrous cap thickness and collagen/elastin content within plaques. Furthermore, exercise training decreased the concentrations of VE-cadherin, MMP-8 and MMP-9, while increasing the concentrations of TIMP-1 and TIMP-2 within the plaques.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Xiaorui Li, Xiao Li, Rong Sun, Mei Gao, Hui Wang
Summary: Cadmium exposure enhances the expression of VE-cadherin in vascular endothelial cells via suppression of ROCK signaling.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hsien-Lin Chen, Yu-Chieh Su, Huang-Chi Chen, Jui-Hsin Su, Chang-Yi Wu, Shih-Wei Wang, In-Pin Lin, Chung-Yi Chen, Chien-Hsing Lee
Summary: The study focused on investigating the anti-lymphangiogenic effect of heteronemin (SP-1) from a sponge in human lymphatic endothelial cells (LECs) and in vivo models. Results showed that SP-1 inhibits lymphangiogenesis by downregulating the VEGFR-3 cascade, ARF-1, and MMP-9/VE-cadherin/vimentin pathways. These findings suggest that SP-1 could be a potential candidate for treating lymphangiogenesis-associated diseases.
Article
Cell & Tissue Engineering
Violetta A. Maltabe, Anna N. Melidoni, Dimitris Beis, Ioannis Kokkinopoulos, Nikolaos Paschalidis, Panos Kouklis
Summary: The study found that ISL1+ cardiovascular progenitor cells form adherens junctions through VE-CADHERIN during differentiation, which is crucial for cardiac differentiation.
Article
Cell & Tissue Engineering
Mariko Tsuruda, Saori Morino-Koga, Minetaro Ogawa
Summary: Experimental findings suggest that VE-cad(+) cells from late-stage embryos can differentiate into MCs independently of HSCs in vitro, and have the potential to generate connective tissue MCs in vivo, shedding light on the differentiation mechanism of hematopoietic cells.
Article
Biochemistry & Molecular Biology
Carole Luthold, Alice-Anais Varlet, Herman Lambert, Francois Bordeleau, Josee N. Lavoie
Summary: The study reveals that during mitosis, BAG3 interacts with HSPB8, p62/SQSTM1, and HDAC6 to regulate cell rounding, cortex stability, and spindle orientation. Depletion of BAG3 affects subcortical actin cloud dynamics and impairs spindle positioning. These effects can be corrected by drugs inhibiting the Arp2/3 complex or HDAC6 activity, indicating a role for BAG3 in tuning branched actin network assembly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Paul Taufalele, Wenjun Wang, Alan J. Simmons, Austin N. Southard-Smith, Bob Chen, Joshua D. Greenlee, Michael R. King, Ken S. Lau, Duane C. Hassane, Francois Bordeleau, Cynthia A. Reinhart-King
Summary: Intratumor heterogeneity plays a crucial role in cancer therapy, and the mechanisms of cell-cell interactions are still unclear. This study investigated the transcriptional differences between tumors with different stiffness using single-cell RNA sequencing. It was found that tumors with higher stiffness had a higher concentration of tumor-promoting macrophages. These findings highlight the importance of cell-cell interactions and macrophage recruitment in tumor development.
ACTA BIOMATERIALIA
(2023)
Article
Multidisciplinary Sciences
Matthew R. Zanotelli, Jian Zhang, Ismael Ortiz, Wenjun Wang, Neil C. Chada, Cynthia A. Reinhart-King
Summary: The study found that changes in collagen density are correlated with cell migration ability and bioenergetics, with significantly different effects observed in highly motile cells. These results reveal a link between matrix mechanics, migratory phenotype, and bioenergetics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Martial Millet, Enola Bollmann, Cassandra Ringuette Goulet, Genevieve Bernard, Stephane Chabaud, Marc-Etienne Huot, Frederic Pouliot, Stephane Bolduc, Francois Bordeleau
Summary: A study on the physical properties of tumors demonstrates that a 3D self-assembly bladder model constructed with cancer-associated fibroblasts can effectively recapitulate the biological and mechanical features of tumors. The model exhibited increased extracellular matrix content, remodeling, and stiffness in the stroma assembled by cancer-associated fibroblasts. Additionally, normal urothelial cells seeded on the tumor model displayed tumor-like responses, including increased cell proliferation, cell infiltration, and features of epithelial-to-mesenchymal transition.
Review
Oncology
Carole Luthold, Tarek Hallal, David P. Labbe, Francois Bordeleau
Summary: Prostate cancer affects a large number of men worldwide. Understanding the mechanisms of disease progression and therapy resistance is crucial for developing effective treatments. Alterations in the extracellular matrix, particularly stiffening, play a role in prostate cancer progression. This review examines the association between extracellular matrix stiffening and disease progression and castration resistance in prostate cancer.
Article
Biology
Samantha C. Schwager, Katherine M. Young, Lauren A. Hapach, Caroline M. Carlson, Jenna A. Mosier, Tanner J. McArdle, Wenjun Wang, Curtis Schunk, Anissa L. Jayathilake, Madison E. Bates, Francois Bordeleau, Marc A. Antonyak, Richard A. Cerione, Cynthia A. Reinhart-King
Summary: Weakly migratory cancer cells disseminate from the primary tumor via communication with stromal cells and enhance cancer cell migration and metastasis by releasing microvesicles rich in Tg2.
Article
Multidisciplinary Sciences
Wenjun Wang, Lauren A. Hapach, Lauren Griggs, Kyra Smart, Yusheng Wu, Paul V. Taufalele, Matthew M. Rowe, Katherine M. Young, Madison E. Bates, Andrew C. Johnson, Nicholas J. Ferrell, Ambra Pozzi, Cynthia A. Reinhart-King
Summary: This study investigates the interplay between diabetes and breast cancer, focusing on the mechanistic role of extracellular matrix stiffening. Using a murine model, in vitro systems, and patient samples, the study reveals that hyperglycemia promotes tumor growth, extracellular matrix stiffness, glycation, and the epithelial-mesenchymal transition of tumor cells. Inhibition of glycation or mechanotransduction effectively reduces these metrics in diabetic mice, suggesting that glycation inhibition could be a potential adjuvant therapy for diabetic cancer patients.
Article
Cell Biology
Leo Piquet, Kelly Coutant, Andrew Mitchell, Amel Ben Anes, Enola Bollmann, Nathan Schoonjans, Julie Berube, Francois Bordeleau, Alain Brisson, Solange Landreville
Summary: This study investigates the effects of extracellular vesicles (EVs) released by uveal melanoma (UM) cells on stellate and endothelial cells in the tumor microenvironment. The findings show that UM-derived EVs lead to increased contractility in hepatic stellate cells and promote the formation of capillary-like networks in endothelial cells.
Article
Cell Biology
Wenjun Wang, Paul V. Taufalele, Martial Millet, Kevin Homsy, Kyra Smart, Emily D. Berestesky, Curtis T. Schunk, Matthew M. Rowe, Francois Bordeleau, Cynthia A. Reinhart-King
Summary: This study reveals that matrix stiffness promotes tumor cell intravasation by increasing MENA expression and decreasing ESRP1 expression, leading to enhanced contractility and intravasation.
Article
Cell Biology
You Chi Tang, Khoren Ponsin, Adda-Lee Graham-Paquin, Carole Luthold, Kevin Homsy, Magdalena Schindler, Viviane Tran, Jean-Francois Cote, Francois Bordeleau, Anmar Khadra, Maxime Bouchard
Summary: During urinary tract development, the common nephric duct (CND) undergoes shortening through non-professional efferocytosis, where apoptotic bodies are engulfed by epithelial cells. This process, coupled with actomyosin contractility, ensures CND shortening without compromising the structural connection between the ureter and bladder. Disruption of apoptosis, non-professional efferocytosis, or actomyosin activity leads to deficient CND shortening. These findings highlight the importance of non-professional efferocytosis and actomyosin contractility in controlling CND morphogenesis.
Editorial Material
Oncology
Francois Bordeleau
Summary: Despite progress, reliable tools for predicting tumor aggressiveness, including prostate cancer, are still lacking. Biomarkers have poor accuracy when used alone due to tumor heterogeneity. However, TP53 mutations are highly correlated with progression.
Meeting Abstract
Biophysics
Martial Millet, Emilie Pic, Carole Luthold, Gaelle Bourriquen, Gabriel Khelifi, Samer Hussein, Francois Bordeleau.
BIOPHYSICAL JOURNAL
(2023)
Article
Chemistry, Physical
Matthew M. Rowe, Wenjun Wang, Paul Taufalele, Cynthia A. Reinhart-King
Summary: Diabetes is associated with increased risk of breast cancer and worse prognoses for cancer patients. Hyperglycemia leads to increased accumulation of AGEs and stiffening of collagen matrix, resulting in increased cancer cell spreading and migration. Treatment with an AGE-breaking drug can reduce AGE accumulation, decrease matrix stiffness, and inhibit cell migration.