Browsing by Author "Contreras, O."

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    Clinical and molecular characterization of Chilean patients with X-linked hypophosphatemia
    (2021) Jimenez, M.; Ivanovic-Zuvic, D.; Loureiro, C.; Carvajal, C. A.; Cavada, G.; Schneider, P.; Gallardo, E.; Garcia, C.; Gonzalez, G.; Contreras, O.; Collins, M. T.; Florenzano, P.
    We report the most comprehensive clinical and molecular characterization of XLH patients performed in Chile. We show high prevalence of musculoskeletal burden and pain, associated with significantly impaired physical capacity and quality of life, with many relevant complications presenting more frequently than previously reported in cohorts from developed countries. Introduction Our current understanding of the clinical presentation and natural history of X-linked hypophosphatemia (XLH) comes mainly from cohorts from developed countries, with limited data on the clinical and genetic abnormalities of XLH patients in South America. Objective To describe the clinical, biochemical, and molecular presentation of patients with XLH in Chile. Methods Patients with XLH referred by endocrinologist throughout Chile were included. Demographic data and clinical presentation were obtained from a clinical interview. Surveys were applied for quality of life (QoL), pain, and functionality. FGF23 was measured by ELISA, and genetic testing was performed. Imaging studies were conducted to assess skeletal and renal involvement. Results We included 26 patients, aged 2-64 years, from 17 unrelated Chilean families. All pediatric patients but only 40% of adults were receiving conventional therapy, while 65% of all patients had elevated alkaline phosphatase. All patients had mutations in PHEX, including 5 novel variants. Radiographic skeletal events (RSE) and enthesopathies in adults were frequent (34% and 85%, respectively). The duration of treatment was associated with fewer RSE (p < 0.05). Most adults reported pain and impaired QoL, and 50% had impaired physical capacity. The number of enthesopathies was associated with worse pain and stiffness scores (p < 0.05). Conclusion Chilean patients with XLH have a high prevalence of musculoskeletal burden associated with pain and impaired physical capacity and QoL, especially in adults who were generally undertreated. These data identify a significant unmet need, inform our understanding of the current status of patients, and can guide care for XLH patients in similarly socioeconomically defined countries.
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    Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction
    (2022) Janbandhu, V.; Tallapragada, V.; Patrick, R.; Li, Y.; Abeygunawardena, D.; Humphreys, D.T.; Martin, E.M.M.A.; Ward, A.O.; Contreras, O.; Farbehi, N.; Yao, E.; Du, J.; Dunwoodie, S.L.; Bursac, N.; Harvey, R.P.
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    PDGF-PDGFR network differentially regulates the fate, migration, proliferation, and cell cycle progression of myogenic cells
    (2021) Contreras, O.; Córdova-Casanova, A.; Brandan, E.
    Platelet-derived growth factors (PDGFs) regulate embryonic development, tissue regeneration, and wound healing through their binding to PDGF receptors, PDGFR alpha and PDGFR beta. However, the role of PDGF signaling in regulating muscle development and regeneration remains elusive, and the cellular and molecular responses of myogenic cells are understudied. Here, we explore the PDGF-PDGFR gene expression changes and their involvement in skeletal muscle myogenesis and myogenic fate. By surveying bulk RNA sequencing and single-cell profiling data of skeletal muscle stem cells, we show that myogenic progenitors and muscle stem cells differentially express PDGF ligands and PDGF receptors during myogenesis. Quiescent adult muscle stem cells and myoblasts preferentially express PDGFR beta over PDGFR alpha. Remarkably, cell culture- and injury-induced muscle stem cell activation altered PDGF family gene expression. In myoblasts, PDGF-AB and PDGF-BB treatments activate two pro-chemotactic and pro-mitogenic downstream transducers, RAS-ERK1/2 and PI3K-AKT. PDGFRs inhibitor AG1296 inhibited ERK1/2 and AKT activation, myoblast migration, proliferation, and cell cycle progression induced by PDGF-AB and PDGF-BB. We also found that AG1296 causes myoblast G0/G1 cell cycle arrest. Remarkably, PDGF-AA did not promote a noticeable ERK1/2 or AKT activation, myoblast migration, or expansion. Also, myogenic differentiation reduced the expression of both PDGFR alpha and PDGFR beta, whereas forced PDGFR alpha expression impaired myogenesis. Thus, our data highlight PDGF signaling pathway to stimulate satellite cell proliferation aiming to enhance skeletal muscle regeneration and provide a deeper understanding of the role of PDGF signaling in non-fibroblastic cells.
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    Systems approach identifies TGA1 and TGA4 transcription factors as important regulatory components of the nitrate response of Arabidopsis thaliana roots
    (2014) Alvarez, J.; Riveras Hernández, Eleodoro Javier; Vidal Olate, Elena Alejandra; Gras, Diana; Contreras, O.; Tamayo, K.; Aceituno, F.; Gómez, Isabel; Ruffel, S.; Lejay, L.; Jordana, X.; Gutiérrez Ilabaca, Rodrigo Antonio