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CASTILLO BENNETT, JIMENA VICTORIA
Preferred name
CASTILLO BENNETT, JIMENA VICTORIA
Main Affiliation
Email
jimenacastillob@gmail.com
ORCID
0000-0001-8651-7083
Scopus Author ID
55985592200
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Item type:Publication, Caveolin-1-Mediated Tumor Suppression Is Linked to Reduced HIF1α S-Nitrosylation and Transcriptional Activity in Hypoxia(2020) ;Carlos Sanhueza; ;Manuel Valenzuela-Valderrama ;Pamela ContrerasLorena Lobos-González<jats:p>Caveolin-1 (CAV1) is a well-established nitric oxide synthase inhibitor, whose function as a tumor suppressor is favored by, but not entirely dependent on, the presence of E-cadherin. Tumors are frequently hypoxic and the activation of the hypoxia-inducible factor-1α (HIF1α) promotes tumor growth. HIF1α is regulated by several post-translational modifications, including S-nitrosylation. Here, we evaluate the mechanisms underlying tumor suppression by CAV1 in cancer cells lacking E-cadherin in hypoxia. Our main findings are that CAV1 reduced HIF activity and Vascular Endothelial Growth Factor expression in vitro and in vivo. This effect was neither due to reduced HIF1α protein stability or reduced nuclear translocation. Instead, HIF1α S-nitrosylation observed in hypoxia was diminished by the presence of CAV1, and nitric oxide synthase (NOS) inhibition by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) reduced HIF1α transcriptional activity in cells to the same extent as observed upon CAV1 expression. Additionally, arginase inhibition by (S)-(2-Boronoethyl)-L-cysteine (BEC) partially rescued cells from the CAV1-mediated suppression of HIF1α transcriptional activity. In vivo, CAV1-mediated tumor suppression was dependent on NOS activity. In summary, CAV1-dependent tumor suppression in the absence of E-cadherin is linked to reduced HIF1α transcriptional activity via diminished NOS-mediated HIF1α S-nitrosylation.</jats:p>Scopus© Citations 10 1 3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions(2023); ;Evelyng Catalán ;Gabriel Garrido ;Pilar Morandé<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the <jats:italic>COL7A1</jats:italic> gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients’ chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.</jats:p> </jats:sec>Scopus© Citations 1 1 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Epidemiology of epidermolysis bullosa in Chile(2024); ; ;Cristóbal Lecaros ;Susanne KrämerConstanza Fuentes<jats:p>In this manuscript we are presenting the first National Epidermolysis Bullosa Epidemiology study done in South America. Our manuscript describes not only population-level estimates, such as incidence, prevalence and mortality of EB, but also genetic data that are unique to this underrepresented population. We report new data about this rare disease showing comparable life expectancy to wealthier nations, demonstrating the value of specialized EB care centres.</jats:p>Scopus© Citations 3 13 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Absence of tongue papillae as a clinical criterion for the diagnosis of generalized recessive dystrophic epidermolysis bullosa types(2020) ;Susanne Krämer; ; ;Carolina EncinaJosé Farfán1Scopus© Citations 9 2