Browsing by MeSH term "Extracellular Matrix Proteins"
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Publication HDAC1/2 control mesothelium/ovarian cancer adhesive interactions impacting on Talin-1-α5β1-integrin-mediated actin cytoskeleton and extracellular matrix protein remodeling.(BioMed Central (BMC), 2024-01-23) Terri, Michela; Sandoval, Pilar; Bontempi, Giulio; Montaldo, Claudia; Tomero-Sanz, Henar; de Turris, Valeria; Trionfetti, Flavia; Pascual-Antón, Lucía; Clares-Pedrero, Irene; Battistelli, Cecilia; Valente, Sergio; Zwergel, Clemens; Mai, Antonello; Rosanò, Laura; del Pozo, Miguel Angel; Sánchez-Álvarez, Miguel; Cabañas, Carlos; Tripodi, Marco; López-Cabrera, Manuel; Strippoli, Raffaele; Unión Europea. Comisión Europea. NextGenerationEU; Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Asociación Española Contra el Cáncer; Fundación La Marató TV3; Comunidad de Madrid (España); Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)BACKGROUND Peritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment of adhesive interactions between cancer cells and the peritoneal membrane. Interrelations between EOC and the mesothelial stroma are critical to facilitate the metastatic process. No data is available so far on the impact of histone acetylation/deacetylation, a potentially relevant mechanism governing EOC metastasis, on mesothelial cells (MCs)-mediated adhesion. METHODS Static adhesion and peritoneal clearance experiments were performed pretreating mesenchymal-like MCs and platinum-sensitive/resistant EOC cell lines with MS-275-a Histone deacetylase (HDAC)1-3 pharmacological inhibitor currently used in combination trials. Results were acquired by confocal microscopy and were analyzed with an automated Opera software. The role of HDAC1/2 was validated by genetic silencing. The role of α4-, α5-α1 Integrins and Fibronectin-1 was validated using specific monoclonal antibodies. Quantitative proteomic analysis was performed on primary MCs pretreated with MS-275. Decellularized matrices were generated from either MS-275-exposed or untreated cells to study Fibronectin-1 extracellular secretion. The effect of MS-275 on β1 integrin activity was assessed using specific monoclonal antibodies. The role of Talin-1 in MCs/EOC adhesion was analyzed by genetic silencing. Talin-1 ectopic expression was validated as a rescue tool from MS-275-induced phenotype. The in vivo effect of MS-275-induced MC remodeling was validated in a mouse model of peritoneal EOC dissemination. RESULTS Treatment of MCs with non-cytotoxic concentrations of MS-275 caused a consistent reduction of EOC adhesion. Proteomic analysis revealed several pathways altered upon MC treatment with MS-275, including ECM deposition/remodeling, adhesion receptors and actin cytoskeleton regulators. HDAC1/2 inhibition hampered actin cytoskeleton polymerization by downregulating actin regulators including Talin-1, impairing β1 integrin activation, and leading to abnormal extracellular secretion and distribution of Fibronectin-1. Talin-1 ectopic expression rescued EOC adhesion to MS-275-treated MCs. In an experimental mouse model of metastatic EOC, MS-275 limited tumor invasion, Fibronectin-1 secretion and the sub-mesothelial accumulation of MC-derived carcinoma-associated fibroblasts. CONCLUSION Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.Publication Lymphoangiocrine signals promote cardiac growth and repair.(Nature Publishing Group, 2020-12) Liu, Xiaolei; De la Cruz, Ester; Gu, Xiaowu; Balint, Laszlo; Oxendine-Burns, Michael; Terrones, Tamara; Ma, Wanshu; Kuo, Hui-Hsuan; Lantz, Connor; Bansal, Trisha; Thorp, Edward; Burridge, Paul; Jakus, Zoltán; Herz, Joachim; Cleaver, Ondine; Torres, Miguel; Oliver, Guillermo; Ministerio de Educación (España); European Molecular Biology Organization; Ministerio de Ciencia e Innovación (España); National Institutes of Health (Estados Unidos)Recent studies have suggested that lymphatics help to restore heart function after cardiac injury1-6. Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction. Embryos that lack LECs develop smaller hearts as a consequence of reduced cardiomyocyte proliferation and increased cardiomyocyte apoptosis. Culturing primary mouse cardiomyocytes in LEC-conditioned medium increases cardiomyocyte proliferation and survival, which indicates that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function.Publication Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2.(Elsevier, 2005-03-01) Murga, Matilde; Fernandez-Capetillo, Oscar; Tosato, GiovannaNeuropilin-1 (NRP-1) is a type 1 membrane protein that binds the axon guidance factors belonging to the class-3 semaforin family. In endothelial cells, NRP-1 serves as a co-receptor for vascular endothelial growth factor (VEGF) and regulates VEGF receptor 2 (VEGFR-2)-dependent angiogenesis. Although gene-targeting studies documenting embryonic lethality in NRP-1 null mice have demonstrated a critical role for NRP-1 in vascular development, the activities of NRP-1 in mature endothelial cells have been incompletely defined. Using RNA interference-mediated silencing of NRP-1 or VEGFR-2 in primary human endothelial cells, we confirm that NRP-1 modulates VEGFR-2 signaling-dependent mitogenic functions of VEGF. Importantly, we now show that NRP-1 regulates endothelial cell adhesion to extracellular matrix proteins independently of VEGFR-2. Based on its dual role as an enhancer of VEGF activity and a mediator of endothelial cell adhesiveness described here, NRP-1 emerges as a promising molecular target for the development of antiangiogenic drugs.Publication Validation of the 1,4-butanediol thermoplastic polyurethane as a novel material for 3D bioprinting applications(Wiley, 2020-10-20) Chocarro-Wrona, Carlos; de Vicente, Juan; Antich, Cristina; Jiménez, Gema; Martínez-Moreno, Daniel; Carrillo, Esmeralda; Montañez, Elvira; Gálvez-Martín, Patricia; Perán, Macarena; López-Ruiz, Elena; Marchal, Juan Antonio; [Chocarro-Wrona,C; Antich,C; Jiménez,G; Martínez-Moreno,D; Carrillo,E; Perán,M; López-Ruiz,E; Marchal,JA] Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada-University of Granada, Granada, Spain. [Chocarro-Wrona,C; Antich,C; Jiménez,G; Martínez-Moreno,D; Carrillo,E; Perán,M; López-Ruiz,E; Marchal,JA] Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain. [Chocarro-Wrona,C; Antich,C; Martínez-Moreno,D; Carrillo,E; Marchal,JA] Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain. [Chocarro-Wrona,C; de Vicente,J; Antich,C; Jiménez,G; Martínez-Moreno,D; Carrillo,E; Perán,M; López-Ruiz,E; Marchal,JA] Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain. [de Vicente,J] Department of Applied Physics, Faculty of Sciences, University of Granada, Granada, Spain. [Montañez,E] Biomedical Research Institute of Málaga (IBIMA), Málaga. [Montañez,E] Department of Orthopedic Surgery and Traumatology, Virgen de la Victoria University Hospital, Málaga, Spain. [Gálvez-Martín,P] Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Granada, Spain. [Gálvez-Martín,P] Advanced Therapies Area, Bioibérica S.A.U, Barcelona, Spain. [Perán,M; López-Ruiz,E] Department of Health Sciences, University of Jaén, Jaén, SpainTissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage-like mechanical properties capable of sustaining high load-bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the novel 1,4-butanediol thermoplastic polyurethane elastomer (b-TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE. The mechanical behavior of b-TPUe in terms of friction and elasticity were examined and compared with human articular cartilage, PCL, and PLA. Moreover, infrapatellar fat pad-derived human mesenchymal stem cells (MSCs) were bioprinted together with scaffolds. in vitro cytotoxicity, proliferative potential, cell viability, and chondrogenic differentiation were analyzed by Alamar blue assay, SEM, confocal microscopy, and RT-qPCR. Moreover, in vivo biocompatibility and host integration were analyzed. b-TPUe demonstrated a much closer compression and shear behavior to native cartilage than PCL and PLA, as well as closer tribological properties to cartilage. Moreover, b-TPUe bioprinted scaffolds were able to maintain proper proliferative potential, cell viability, and supported MSCs chondrogenesis. Finally, in vivo studies revealed no toxic effects 21 days after scaffolds implantation, extracellular matrix deposition and integration within the surrounding tissue. This is the first study that validates the biocompatibility of b-TPUe for 3D bioprinting. Our findings indicate that this biomaterial can be exploited for the automated biofabrication of artificial tissues with tailorable mechanical properties including the great potential for cartilage TE applications.