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Fernández Martos, Sandra

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Sandra

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Fernández Martos

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Ciencias Experimentales

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2018 - 201932020 - 20212
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Now showing 1 - 5 of 5
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    Intrinsic activation of cell growth and differentiation in ex vivo cultured human hair follicles by a transient endogenous production of ROS.
    (Scientific reports, 2019) Calvo Sánchez, María Inmaculada; Fernández Martos, Sandra; Montoya, Juan José; Espada, Jesús
    The emerging variety of signalling roles for ROS in eukaryotic cells and tissues is currently a matter of intense research. Here we make use of ex vivo cultured single human hair follicles as an experimental model to demonstrate that a transient production of non-lethal endogenous ROS levels in these mini-organs promotes efficiently the entry into the growth phase (anagen). The stimulatory process implicates the specific activation of the hair follicle stem cell niche, encompassing the induction of stem cell differentiation markers (Ck15), overall cell proliferation and sustained growth of the tissue associated with expression of gen targets (Ccnd1) concomitant with the inhibition of Wnt signaling antagonists and repressors (Dkk1, Gsk3β) of Wnt signaling. As a whole, this observation indicates that, once activated, ROS signalling is an intrinsic mechanism regulating the hair follicle stem cell niche independently of any external signal.
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    The deleterious effects induced by an acute exposure of human skin to common air pollutants are prevented by extracts of Deschampsia antarctica.
    (Scientific Reports, 2021) Fernández Martos, Sandra; Calvo Sánchez, María Inmaculada; Lobo Aldezabal, Ana; Sánchez Adrada, Ana Isabel; Moreno, Carmen; Vitale, María; Espada, Jesús
    The homeostatic and regenerative potential of the skin is critically impaired by an increasing accumulation of air pollutants in human ecosystems. These toxic compounds are frequently implicated in pathological processes such as premature cutaneous ageing, altered pigmentation and cancer. In this scenario, innovative strategies are required to tackle the effects of severe air pollution on skin function. Here we have used a Human Skin Organotypic Culture (HSOC) model to characterize the deleterious effects of an acute topic exposure of human skin to moderately high concentrations of common ambient pollutants, including As, Cd, Cr, dioxins and tobacco smoke. All these toxic compunds inflict severe damage in the tissue, activating the AHR-mediated response to xenobiotics. We have further evaluated the potential of an aqueous leaf extract of the polyextremophile plant Deschampsia antarctica (Edafence) to protect human skin against the acute exposure to toxic pollutants. Our results indicate that pre-treatment of HSOC samples with this aqueous extract conuterbalances the deleterious effects of the exposure to toxic comunds and triggers the activation of key genes invoved in the redox system and in the pro-inflammatory/wound healing response in the skin, suggesting that this natural compound might be effectively used in vivo to protect human skin routinely in different daily conditions.
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    Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Pho togeneration of Reactive Oxygen Species In Situ.
    (Journal of Visualized Experiments, 2020) Espada, Jesús; Carrasco, Elisa; Calvo Sánchez, María Inmaculada; Fernández Martos, Sandra; Montoya, Juan José
    Here, we describe a protocol to induce switchable in vivo photogeneration of endogenous reactive oxygen species (ROS) in mouse skin. This transient production of ROS in situ efficiently activates cell proliferation in stem cell niches and stimulates tissue regeneration as strongly manifested through the acceleration of burn healing and hair follicle growth processes. The protocol is based on a regulatable photodynamic treatment that treats the tissue with precursors of the endogenous photosensitizer protoporphyrin IX and further irradiates the tissue with red light under tightly controlled physicochemical parameters. Overall, this protocol constitutes an interesting experimental tool to analyze ROS biology.
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    Sustained Human Hair Follicle Growth Ex Vivo in a Glycosaminoglycan Hydrogel Matrix.
    (International Journal of Molecular Sciences, 2019) Fernández Martos, Sandra; Calvo Sánchez, María Inmaculada; García Alonso, Karla; Castro, Begoña; Hashtroody, Bita; Espada, Jesús
    Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes (e.g., wound repair) of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Here we report that growing human hair follicles ex vivo in a defined GAG hydrogel mimicking the dermal matrix strongly promotes sustained cell survival and maintenance of a highly proliferative phenotype in the hair bulb and suprabulbar regions. This significant effect is associated with the activation of WNT/β-catenin signaling targets (CCDN1, AXIN2) and with the expression of stem cell markers (CK15, CD34) and growth factors implicated in the telogen/anagen transition (TGFβ2, FGF10). As a whole, these results point to the dermal GAG matrix as an important component in the regulation of the human hair follicle growth cycle, and to GAG-based hydrogels as potentially relevant modulators of this process both in vitro and in vivo.
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    A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle.
    (Journal of Molecular Cell Biology, 2018) Calvo Sánchez, María Inmaculada; Fernández Martos, Sandra; Carrasco, Elisa; Moreno Bueno, Gema; Bernabéu, Carmelo; Quintanilla, Miguel; Espada, Jesús
    The hair follicle is a biological oscillator that alternates growth, regression, and rest phases driven by the sequential activation of the proliferation/differentiation programs of resident stem cell populations. The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling, while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity. A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways. Here we have focused on the role of Endoglin (Eng), a key co-receptor for members of the Tgf-β/Bmp family of growth factors. Using an Eng haploinsufficient mouse model, we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell niches. We further report that β-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that β-catenin interacts with Smad4 in a Bmp/Eng-dependent context and both proteins act synergistically to activate Eng promoter transcription. These observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback cross-talk between Wnt/β-catenin and Bmp/Smad signals.