Review
Biochemistry & Molecular Biology
Iason Psilopatis, Eleni Souferi-Chronopoulou, Kleio Vrettou, Constantinos Troungos, Stamatios Theocharis
Summary: EPHs/ephrins appear to be promising treatment targets in the future for breast cancer, with EPHA2 being the most studied target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Iason Psilopatis, Ioannis Karniadakis, Konstantinos Stylianos Danos, Kleio Vrettou, Kleita Michaelidou, Konstantinos Mavridis, Sofia Agelaki, Stamatios Theocharis
Summary: Lung cancer is the leading cause of cancer death in the United States. Erythropoietin-producing hepatocellular receptors (EPHs) and their ligands ephrins play a defining role in the development and progression of lung cancer. Targeting EPHs/ephrins may provide effective treatment options for precision cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
David G. Wilkinson
Summary: Cell segregation to form sharp boundaries is crucial for stabilizing tissue organization and is driven by differential adhesion mediated by cadherins and Eph receptor/ephrin signaling regulating cell adhesion, cortical tension, and repulsion. These mechanisms interplay with cadherins antagonizing homotypic tension within cell populations and Eph receptors mainly driving segregation through increased heterotypic tension or repulsion. The differential tension between homotypic and heterotypic tensions ultimately leads to cell segregation and border sharpening.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Junhao Lin, Chunting Zeng, JiaKang Zhang, Zhenghui Song, Na Qi, Xinhui Liu, Ziyan Zhang, Aimin Li, Fengsheng Chen
Summary: EFNA4 plays a crucial role in promoting proliferation and migration of HCC cells, and its overexpression is associated with poor prognosis. EFNA4 regulates the PIK3R2/GSK3 beta/beta-catenin loop to influence the survival and migration of HCC cells.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Biochemistry & Molecular Biology
Sakshi Arora, Andrew M. Scott, Peter W. Janes
Summary: Eph receptor tyrosine kinases play critical roles in development and tissue formation, and are regulated by membrane-bound ligands ephrins. They have low expression in adults, but are often overexpressed in cancers, where they are associated with tumour development, vasculature, and invasion. Understanding the opposing roles of Ephs in different cancers is crucial for developing targeted therapies.
Review
Reproductive Biology
Enoch Appiah Adu-Gyamfi, Armin Czika, Tai-Hang Liu, Philip Narteh Gorleku, Linda Ahenkorah Fondjo, Francis Tanam Djankpa, Yu-Bin Ding, Ying-Xiong Wang
Summary: Ephrins and Eph receptors play important roles in the female reproductive system, regulating various processes and being associated with obstetric and gynecologic disorders.
BIOLOGY OF REPRODUCTION
(2021)
Article
Chemistry, Medicinal
Maricel Gomez-Soler, Erika J. Olson, Elena Rubio de la Torre, Chunxia Zhao, Ilaria Lamberto, Dillon T. Flood, Waleed Danho, Bernhard C. Lechtenberg, Stefan J. Riedl, Elena B. Pasquale, Philip E. Dawson
Summary: The EphA4 receptor tyrosine kinase is involved in several diseases and inhibiting its activity could have therapeutic potential. Researchers have identified a peptide antagonist that specifically inhibits the binding of ephrin ligands to EphA4. They have also modified the peptide to improve its stability and activity. These derivatives could be useful for studying EphA4 in vivo and for testing EphA4 inhibition in animal models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Radoslaw Kaczmarek, Katarzyna Zimmer, Pawel Gajdzis, Malgorzata Gajdzis
Summary: The cornea, though simple in appearance, is a highly complex structure that requires perfect organization of cells for maintaining its biomechanical and optical properties. Eph receptors and ephrins play a crucial role in tissue organization, cell migration, and communication, particularly in the regeneration process following injuries and diseases. This review examines the current understanding of Eph and ephrins in corneal physiology and diseases, with a focus on the epithelium and endothelium, as well as their influence on corneal neovascularization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Amita R. Sahoo, Matthias Buck
Summary: This review focuses on the interaction between Eph receptors and ephrin ligands in regulating various processes from embryonic development to tissue homeostasis. It also highlights the importance of the transmembrane domain of Eph receptors in signal transduction and introduces techniques such as NMR and molecular modeling used to study them. Additionally, the use of transmembrane peptides to manipulate Eph receptor signaling is discussed, along with future directions for research in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sho Kohara, Kazushige Ogawa
Summary: Kupffer cells are maintained through self-renewal within liver sinusoidal endothelial cells (LSECs). In this study, liver macrophages (Mo) were propagated from mice using mixed culture with hepatic fibroblastic cells. The propagated liver Mo expressed specific transcription factors and exhibited similar gene expression and surface markers as primary LSECs, suggesting that their properties resemble those of Kupffer cells. Further investigation revealed the expression of certain Eph receptors and ephrin ligands, as well as integrin subunits and corresponding ligands, potentially contributing to the adhesion and residence of Kupffer cells within the liver sinusoid.
Article
Cell Biology
Ace E. Lewis, Akela Kuwahara, Jacqueline Franzosi, Jeffrey O. Bush
Summary: This study reveals the role of the Efnb2 gene in regulating tracheoesophageal separation by controlling the dorsoventral allocation of tracheal-fated cells. It also uncovers the mechanism of how NKX2-1 coordinates tracheal specification with tissue separation through the regulation of EPHRIN-B2 and tracheoesophageal cell sorting.
Article
Biochemistry & Molecular Biology
Priya Jarwar, Shakeel Ahmed Sheikh, Yar Muhammad Waryah, Ikram Uddin Ujjan, Saima Riazuddin, Ali Muhammad Waryah, Zubair M. Ahmed
Summary: Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous, with cataracts segregating in a recessive manner in three families with variability related to age of onset. Exome sequencing identified a novel EPHA2 variant in LUCC03 and a known variant in the other families. Computational modeling predicted that the variants cause misfolding of EPHA2. This study provides insights into the molecular and phenotypic landscape of EPHA2-related HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Debanjan Barua, Rudolf Winklbauer
Summary: In the primitive vertebrate gastrula, the formation of the boundary between the ectoderm and mesoderm is controlled by Brachet's cleft and Eph/ephrin signaling. This signaling pathway regulates cortical tension and cell adhesion, leading to the generation of high interfacial tension and the asymmetric structure of the boundary.
DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Sahibpreet Kaur, Anjana Bali, Nirmal Singh, Amteshwar Singh Jaggi
Summary: Ephrins and Eph receptors play a crucial role in nervous system development, including axon guidance and cell migration. Upregulation of ephrin B1/EphB1 and ephrin B2/EphB2 has been observed in neuropathic pain of different etiology. Activation of the ephrin B/EphB system in the dorsal root ganglion and dorsal horn of the spinal cord may be essential in initiating and maintaining neuropathic pain. Inhibitors of EphB receptors could potentially be used to manage pain symptoms. Ephrin B/EphB-mediated synaptic plasticity involves phosphorylation and activation of NMDA receptors and other molecular mechanisms, including activation of inflammatory cytokines, caspase-3, calpain-1, PI3K, PKA, and CREB. This review discusses the role and molecular mechanisms involved in ephrin B/EphB-mediated neuropathic pain.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Abigail A. Kindberg, Vasudha Srivastava, Jonathon M. Muncie, Valerie M. Weaver, Zev J. Gartner, Jeffrey O. Bush
Summary: The study reveals that EPH/EPHRIN signaling decreases the stability of heterotypic cell:cell contacts through increased cortical actomyosin contractility, driving cellular self-organization. The cell segregation driven by EPH/EPHRIN depends on actomyosin contractility but occurs independently of directed cell migration and without changes in cell adhesion.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Anna Salas, Anna Duarri, Laura Fontrodona, Diana Mora Ramirez, Anna Badia, Helena Isla-Magrane, Barbara Ferreira-de-Souza, Miguel Angel Zapata, Angel Raya, Anna Veiga, Jose Garcia-Arumi
Summary: This study showed that combined transplantation of hiPSC-derived RPE and RPCs is a potentially superior therapeutic approach to protect the retina from degeneration in RDDs. The grafted cells survived in the subretinal space for 12 weeks and rats treated with RPE + RPC therapy exhibited better conservation of the outer nuclear layer and visual response compared to RPE or RPC-treated rats. Transplanted RPE cells integrated into the host RPE layer, while RPC mostly remained in the subretinal space with a limited number of cells integrated into the ONL.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Chemistry, Multidisciplinary
Maria Helena Macedo, Andreia S. Barros, Elena Martinez, Cristina C. Barrias, Bruno Sarmento
Summary: The study aimed to develop an advanced 3D intestinal model for more reliable absorption testing and better mimicking the native environment, unveiling cellular crosstalk between different cells. This model showed lower levels of efflux transporters and improved permeability outcomes compared to traditional models, leading to more accurate results in line with in vivo data.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Cell Biology
Helena Mazuelas, Miriam Magallon-Lorenz, Juana Fernandez-Rodriguez, Itziar Uriarte-Arrazola, Yvonne Richaud-Patin, Ernest Terribas, Alberto Villanueva, Elisabeth Castellanos, Ignacio Blanco, Angel Raya, Jakub Chojnacki, Holger Heyn, Cleofe Romagosa, Conxi Lazaro, Bernat Gel, Meritxell Carrio, Eduard Serra
Summary: In this study, researchers developed an iPSC-based in vitro differentiation system for studying the development of plexiform neurofibromas (pNFs). They found that using a heterotypic spheroid model could generate tumors similar to human pNFs. Additionally, analysis of human pNF single-cell RNA sequences revealed the presence of subpopulations of Schwann cells at different differentiation states.
Article
Materials Science, Multidisciplinary
Laura Clua-Ferre, Francesco De Chiara, Julia Rodriguez-Comas, Jordi Comelles, Elena Martinez, Amelie Luise Godeau, Ainhoa Garcia-Alaman, Rosa Gasa, Javier Ramon-Azcon
Summary: A novel bio-printing procedure is developed to fabricate large amounts of reproducible microspheres capable of secreting insulin. This method overcomes the limitations of traditional microsphere fabrication techniques and provides an efficient way to produce cell-laden microspheres.
ADVANCED MATERIALS TECHNOLOGIES
(2022)
Editorial Material
Cell & Tissue Engineering
Rana Dajani, Bashir Jiwani, Azim Nanji, Laurie Zoloth, Mohammed Ghaly, Ilhan Ilkilic, Angel Raya, Maria Patrao Neves, Helena de Melo, Ana Sofia Carvalho, Timothy Caulfield, Rose Carter, Antonio Rendas, Azim Surani, Janet Rossant, Arnold Kriegstein, El-Nasir Lalani
Summary: Greater engagement from diverse Muslim voices, along with cross-cultural and transdisciplinary collaboration, is necessary to enhance understanding of stem cell science, address ethical complexities, ensure compliance, foster public deliberation, build trust, and improve practice standards.
Article
Cell & Tissue Engineering
Belen Alvarez-Palomo, Anna Veiga, Angel Raya, Margarita Codinach, Silvia Torrents, Laura Ponce Verdugo, Clara Rodriguez-Aierbe, Leopoldo Cuellar, Raquel Alenda, Cristina Arbona, Dolores Hernandez-Maraver, Cristina Fuste, Sergi Querol
Summary: This article describes the process of generating a CD34+ cell product as a starting material to produce HLA-homozygous iPSC following a cost-effective and clinical grade-compliant procedure, starting from unit selection and donor reconsenting. These CD34+ cells serve as the basis for the Spanish bank of haplolines, aimed to provide cell products for clinical research and therapy.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Pharmacology & Pharmacy
Maria Garcia-Diaz, Maria del Mar Cendra, Raquel Alonso-Roman, Maria Urdaniz, Eduard Torrents, Elena Martinez
Summary: The intestinal mucus acts as a barrier on the luminal surface of the intestinal epithelium, providing defense against external insults and supporting the resident microbiota. In a 3D villus-like hydrogel scaffold model, the secreted mucus enhanced adhesion of a pathogenic E. coli strain while also protecting against invasion.
Article
Cardiac & Cardiovascular Systems
Marcos Siguero-Alvarez, Alejandro Salguero-Jimenez, Joaquim Grego-Bessa, Jorge de la Barrera, Donal MacGrogan, Belen Prados, Fernando Sanchez-Saez, Rebeca Pineiro-Sabaris, Natalia Felipe-Medina, Carlos Torroja, Manuel Jose Gomez, Maria Sabater-Molina, Ruben Escriba, Ivonne Richaud-Patin, Olalla Iglesias-Garcia, Mauro Sbroggio, Sergio Callejas, Declan P. O'Regan, Kathryn A. McGurk, Ana Dopazo, Giovanna Giovinazzo, Borja Ibanez, Lorenzo Monserrat, Jose Maria Perez-Pomares, Fatima Sanchez-Cabo, Alberto M. Pendas, Angel Raya, Juan R. Gimeno-Blanes, Jose Luis de la Pompa
Summary: The study reveals that MIB1-NOTCH variants play a crucial role in the development of both LVNC and bicuspid aortic valve, along with other genetic modifiers.
Article
Engineering, Biomedical
Gizem Altay, Aina Abad-Lazaro, Emilio J. Gualda, Jordi Folch, Claudia Insa, Sebastien Tosi, Xavier Hernando-Momblona, Eduard Batlle, Pablo Loza-Alvarez, Vanesa Fernandez-Majada, Elena Martinez
Summary: This study presents a novel 3D in vitro intestinal model based on primary epithelial cells that replicates both villus-like architecture and gradients of ISC biochemical factors. This model opens up possibilities for studying the nature of such gradients and resulting cellular responses in vitro.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Enara Larranaga, Vanesa Fernandez-Majada, Samuel Ojosnegros, Jordi Comelles, Elena Martinez
Summary: Eph-ephrin signaling is important for defining spatial cues in tissue boundaries and cell organization. This study demonstrates that spatial patterns of ephrin ligands can modulate the organization of compartments in intestinal epithelial monolayers. It also shows that ligand concentration and cellular density can impact the strength of the repulsive effect triggered by Eph-ephrin signaling.
ADVANCED MATERIALS INTERFACES
(2022)
Review
Cardiac & Cardiovascular Systems
Maurizio Pesce, Georg N. Duda, Giancarlo Forte, Henrique Girao, Angel Raya, Pere Roca-Cusachs, Joost P. G. Sluijter, Carsten Tschope, Sophie Van Linthout
Summary: A growing body of evidence suggests that the mechanical functions of cardiac fibroblasts, as a necessary component, play an active role in myocardial growth and homeostasis. This review describes cell mechanosensation as a regulator of cardiac maturation and disease, and provides evidence that changes in the mechanical properties of the myocardium can occur due to disease-induced remodeling of the cardiac extracellular matrix.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Ruben Escriba, Jose M. Larranaga-Moreira, Yvonne Richaud-Patin, Lea Pourchet, Ioannis Lazis, Senda Jimenez-Delgado, Alba Morillas-Garcia, Martin Ortiz-Genga, Juan Pablo Ochoa, David Carreras, Guillermo Javier Perez, Jose Luis de la Pompa, Ramon Brugada, Lorenzo Monserrat, Roberto Barriales-Villa, Angel Raya
Summary: This study investigated the genotype-phenotype relationships in two siblings with hypertrophic cardiomyopathy (HCM). The study found that the pathogenic MYBPC3 variant caused impaired mitochondrial bioenergetics and altered excitation-contraction coupling in patient-specific cardiomyocytes. Additionally, a variant in the MYH7 gene was identified as a modifier of HCM expressivity.
CIRCULATION RESEARCH
(2023)
Article
Medicine, Research & Experimental
Alba Tristan-Noguero, Irene Fernandez-Carasa, Carles Calatayud, Cristina Bermejo-Casadesus, Meritxell Pons-Espinal, Arianna Colini Baldeschi, Leticia Campa, Francesc Artigas, Analia Bortolozzi, Rosario Domingo-Jimenez, Salvador Ibanez, Merce Pineda, Rafael Artuch, Angel Raya, Angels Garcia-Cazorla, Antonella Consiglio
Summary: This study used induced pluripotent stem cells (iPSCs) to generate dopaminergic neurons (DAn) from patients with tyrosine hydroxylase deficiency (THD) and compared them with control-DAn. THD iPSC-DAn showed lower levels of dopamine metabolites and reduced TH expression compared to controls. Additionally, THD iPSC-DAn displayed abnormal morphology and neuronal defects, which were rescued by L-Dopa treatment only in the milder form of THD (THD-A). Treatment at the stage of neuronal precursors could prevent the alterations in the severe form of THD (THD-B). This iPSC-based model recapitulates THD disease phenotypes and response to treatment.
EMBO MOLECULAR MEDICINE
(2023)
Article
Engineering, Biomedical
Jordi Comelles, Vanesa Fernandez-Majada, Veronica Acevedo, Beatriz Rebollo-Calderon, Elena Martinez
Summary: Topographical patterns are powerful tools for studying directional cell migration. This study investigates how substrate stiffness affects the cellular response to topographical contact guidance. The results show that both matrix stiffening and alignment of extracellular matrix fibers play a role in directional cell migration, with different outcomes depending on cell type and cytoskeleton organization.
MATERIALS TODAY BIO
(2023)
Article
Nanoscience & Nanotechnology
Sumithra Yasaswini Srinivasan, Marina Cler, Osnat Zapata-Arteaga, Bernhard Dorling, Mariano Campoy-Quiles, Elena Martinez, Elisabeth Engel, Soledad Perez-Amodio, Anna Laromaine
Summary: The low endogenous regenerative capacity of the heart, combined with the prevalence of cardiovascular diseases, has led to the development of cardiac tissue engineering. In this study, a conductive cardiac patch made of bacterial nanocellulose (BC) with polypyrrole nanoparticles (Ppy NPs) was created to mimic the natural myocardial microenvironment. The BC-Ppy scaffolds showed promising properties such as flexibility, 3D extracellular matrix-like structure, and electrical conductivity, making them suitable for use as cardiac patches in tissue regenerative therapies.
ACS APPLIED BIO MATERIALS
(2023)