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  1. Home
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Browsing by Subject "Pericyte"

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    Dataset of the project: Una Posible Diana Terapeutica para Bloquear la Progresión del Glioblastoma: la Autofagia Mediada por Chaperonas en Pericitos (PID2020-114010RB-I00)
    (2026-02-09) Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Valdor Alonso, Rut; Salinas Hidalgo, María Dolores; Bioquímica y Biología Molecular B e Inmunología
    Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome
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    Expression of lumican and osteopontin in perivascular areas of the glioblastoma peritumoral niche and its value for prognosis
    (MDPI, 2024-12-29) Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
    Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome. The secretion of extracellular matrix (ECM) proteins with anti-tumor (Lumican) and pro-tumoral (Osteopontin, OPN) properties was shown to be dependent on the regulation of GB-induced CMA in PCs. As biomarkers are rarely studied in TME, in this work, we aimed to validate Lumican and OPN as prognostic markers in the perivascular areas of the peritumoral niche of a cohort of GB patients. Previously, we had validated their expression in GB xenografted mice presenting GB infiltration (OPN) or GB elimination (Lumican) dependent on competent or deficient CMA PCs, respectively. Then, patient sample classification by GB infiltration into the peritumoral brain parenchyma was related to GB-induced CMA in microvasculature PCs, analyzing the expression of the lysosomal receptor, LAMP-2A. Our results revealed a correlation between GB-induced CMA activity in peritumoral PCs and GB patients’ outcomes, identifying three degrees of severity. The perivascular expression of both immune activation markers, Iba1 and CD68, was related to CMA-dependent PC immune function and determined as useful for efficient GB prognosis. Lumican expression was identified in perivascular areas of patients with less severe outcome and partially co-localizing with PCs presenting low CMA activity, while OPN was primarily found in perivascular areas of patients with poor outcome and partially co-localizing with PCs presenting high CMA activity. Importantly, we found sex differences in the incidence of middle-aged patients, being significantly higher in men but with worse prognosis in women. Our results confirmed that Lumican and OPN in perivascular areas of the GB peritumoral niche are effective predictive biomarkers for evaluating prognosis and monitoring possible therapeutic immune responses dependent on PCs in tumor progression.
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    Leptomeninges: a novel stem cell niche harboring ischemia-induced neural progenitors
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Nakagomi, Takayuki; Nakano-Doi, Akiko; Matsuyama, Tomoiro
    It is well known that neural stem cells (NSCs) are present in many parts of the central nervous system (CNS), including the subventricular zone (SVZ) of the lateral ventricle, subgranular zone (SGZ) of the hippocampal dentate gyrus, cortex, and spinal cord. Using a mouse model of cortical infarction, we demonstrated for the first time that NSCs, which can differentiate into neural lineage cells, could be induced in the meninges (leptomeninges) of ischemic brain areas as well. However, such ischemia-induced NSCs (iNSCs) were not observed in the leptomeninges of non-ischemic areas. This suggests the leptomeninges, which surround the CNS, might be a novel stem cell niche harboring endogenous iNSCs following brain injury. In this review, we introduce the characterization and possible origin of leptomeningeal iNSCs based on our reports and recent findings. We also refer to the potential of leptomeningeal iNSCs for cortical neurogenesis.
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    Pericyte morphology and function
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Yemisci, Muge; Dalkara, Turgay; Alarcón Martínez, Luis
    The proper delivery of blood is essential for healthy neuronal function. The anatomical substrate for this precise mechanism is the neurovascular unit, which is formed by neurons, glial cells, endothelia, smooth muscle cells, and pericytes. Based on their particular location on the vessel wall, morphology, and protein expression, pericytes have been proposed as cells capable of regulating capillary blood flow. Pericytes are located around the microvessels, wrapping them with their processes. Their morphology and protein expression substantially vary along the vascular tree. Their contractibility is mediated by a unique cytoskeleton organization formed by filaments of actin that allows pericyte deformability with the consequent mechanical force transferred to the extracellular matrix for changing the diameter. Pericyte ultrastructure is characterized by large mitochondria likely to provide energy to regulate intracellular calcium concentration and fuel contraction. Accordingly, pericytes with compromised energy show a sustained intracellular calcium increase that leads to persistent microvascular constriction. Pericyte morphology is highly plastic and adapted for varying contractile capability along the microvascular tree, making pericytes ideal cells to regulate the capillary blood flow in response to local neuronal activity. Besides the vascular regulation, pericytes also play a role in the maintenance of the blood-brain/retina barrier, neovascularization and angiogenesis, and leukocyte transmigration. Here, we review the morphological and functional features of the pericytes as well as potential specific markers for the study of pericytes in the brain and retina
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    The role of the pericytes of the adventitial microcirculation in the arterial intimal thickening
    (Murcia : F. Hernández, 1990) Díaz-Flores, Lucio; Valladares, Francisco; Gutiérrez, Ricardo; Varela, Hilda
    Segments of rat femoral arteries, with one collateral each, occluded between ligatures and dissected from surrounding tissue, developed intimal thickening, with or without ligation of their collaterals. Numerous newly-formed capillaries from the surrounding arterial rnicrocirculation growing into the adventitia, tunica media and intimal thickening were demonstrated by means of serial longitudinal sections, predominantly in the ostium of the collateral. When the ligatures were applied without damaging the microcirculation surrounding the artery and the normal continuity of the adventitial vessels was unchanged, earlier presence of intimal thickening was observed. When the fibrous layers of the adventitia were removed at the moment of the arterial ligation, the continuity between newlyformed vessels of the neoadventitia and those growing into the media and neointima was much more evident. It was then noted that the pericytes constituted a major component of the intimal thickening. The introduction of contrast material in rnicrocirculation confirmed the connections between newly-formed adventitial and intimal vessels. At the beginning of the experiment, autoradiographic studies showed an increased DNA synthesis in the cells of preformed postcapillary venules and capillaries of surrounding arterial microcirculation and later in those of the newly-formed vessels growing into the arterial wall. These results indicate that newlyformed capillaries derived from surrounding arterial microcirculation penetrate the wall of the occluded arterial segments and contribute to the intimal thickening formation. It is likely that the pericytes and endothelial cells (EC) of these ingrowing vessels are sources of myointimal cells at the intimal thickening and of endothelium at the luminal surface, respectively.

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