LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Advances in understanding the molecular basis of skin fragility [version 1; referees

    Cristina Has

    F1000Research, Vol

    2 approved]

    2018  Volume 7

    Abstract: Skin fragility refers to a large group of conditions in which the ability of the skin to provide protection against trivial mechanical trauma is diminished, resulting in the formation of blisters, erosions, wounds, or scars. Acquired and physiological ... ...

    Abstract Skin fragility refers to a large group of conditions in which the ability of the skin to provide protection against trivial mechanical trauma is diminished, resulting in the formation of blisters, erosions, wounds, or scars. Acquired and physiological skin fragility is common; genetic disorders are rare but give insight into the molecular mechanisms ensuring skin stability. The paradigm is represented by inherited epidermolysis bullosa. This review is focused on recent advances in understanding the molecular basis of genetic skin fragility, including emerging concepts, controversies, unanswered questions, and opinions of the author. In spite of the advanced knowledge on the genetic causes of skin fragility, the molecular pathology is still expanding. Open questions in understanding the molecular basis of genetic skin fragility are the following: what are the causes of phenotypes which remain genetically unsolved, and what are the molecular modifiers which might explain phenotypic differences among individuals with similar mutations? New mutational mechanisms and new genes have recently been discovered and are briefly described here. Comprehensive next-generation sequencing-based genetic testing improved mutation detection and facilitated the identification of the genetic basis of unclear and new phenotypes. Characterization of the biochemical and cell biological consequences of the genetic variants is challenging and laborious but may represent the basis for personalized therapeutic approaches. Molecular modifiers of skin fragility have been uncovered in particular animal and genetic models but not in larger cohorts of patients. This scientific progress is the basis for revisions of the epidermolysis bullosa classification and for innovative therapeutic approaches designed for this intractable condition.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2018-03-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Junctional Epidermolysis Bullosa

    Irina Condrat / Yinghong He / Rodica Cosgarea / Cristina Has

    Frontiers in Medicine, Vol

    Allelic Heterogeneity and Mutation Stratification for Precision Medicine

    2019  Volume 5

    Abstract: Junctional epidermolysis bullosa (JEB) is a hereditary blistering disease caused by reduced dermal-epidermal adhesion due to deficiencies of one of the proteins, laminin-332, type XVII collagen, integrin α6β4 or integrin α3. Significant progress has been ...

    Abstract Junctional epidermolysis bullosa (JEB) is a hereditary blistering disease caused by reduced dermal-epidermal adhesion due to deficiencies of one of the proteins, laminin-332, type XVII collagen, integrin α6β4 or integrin α3. Significant progress has been achieved in the development of therapies for EB, such as bone-marrow transplantation, local or systemic injections with fibroblasts or mesenchymal stromal cells, readthrough of premature termination codons, or exon skipping. These were tailored in particular for dystrophic EB, which is caused by type VII collagen deficiency and have not yet reached broad clinical practice. Recently, pioneering combined gene and stem cell therapy was successful in treating one boy with junctional EB. Beside these exclusive approaches, no specific therapy to amend the major clinical features, skin and mucosal blistering and non-healing wounds is available to date. Here we extend the mutational spectrum of junctional EB, provide a stratification of COL17A1 mutations and discuss potential molecular therapeutic approaches.
    Keywords junctional epidermolysis bullosa ; collagen XVII ; COL17A1 ; mutation ; premature termination codon ; therapy ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Editorial

    Cristina Has / Kyle T. Amber / Dedee F. Murrell / Philippe Musette / Ralf J. Ludwig

    Frontiers in Medicine, Vol

    Skin Blistering Diseases

    2019  Volume 6

    Keywords skin ; autoimmunity ; hereditary diseases ; pemphigoid ; pemphigus ; epidermolysis bollosa ; Medicine (General) ; R5-920
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease

    Blake R. C. Smith / Alexander Nyström / Cameron J. Nowell / Ingrid Hausser / Christine Gretzmeier / Susan J. Robertson / George A. Varigos / Cristina Has / Johannes S. Kern / Ken C. Pang

    Disease Models & Mechanisms, Vol 14, Iss

    2021  Volume 6

    Abstract: Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and ...

    Abstract Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa. This article has an associated First Person interview with the first author of the paper.
    Keywords epidermolysis bullosa ; mouse model ; skin ; blistering ; Medicine ; R ; Pathology ; RB1-214
    Subject code 616
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Emergency management in epidermolysis bullosa

    Jemima E. Mellerio / Maya El Hachem / Nathalia Bellon / Giovanna Zambruno / Hana Buckova / Rudolf Autrata / Carmen Salavastru / Tamara Caldaro / Celine Greco / Cristina Has / Christine Bodemer

    Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-

    consensus clinical recommendations from the European reference network for rare skin diseases

    2020  Volume 10

    Abstract: Abstract Epidermolysis bullosa (EB) comprises a group of genetic disorders with the hallmark of fragility of the skin and mucosal surfaces. The severity of different types of EB varies markedly as does the occurrence of extra-cutaneous involvement and ... ...

    Abstract Abstract Epidermolysis bullosa (EB) comprises a group of genetic disorders with the hallmark of fragility of the skin and mucosal surfaces. The severity of different types of EB varies markedly as does the occurrence of extra-cutaneous involvement and complications. A number of emergency situations may occur in the context of EB including obstruction to oral intake from oral or esophageal blisters or scarring, acute airway obstruction, acute urinary retention, sepsis and corneal erosions. Whilst general management principles apply in each of these settings, specific considerations are essential in managing EB to avoid undue trauma or damage to delicate tissues. These recommendations have been developed from a literature review and consensus from experts of the European Network for Rare Skin Disorders (ERN-Skin) to aid decision-making and optimize clinical care by non-EB expert health professionals encountering emergency situations in babies, children and adults with EB.
    Keywords Epidermolysis bullosa ; Blister ; Esophageal obstruction ; Airway obstruction ; Corneal erosion ; Urinary retention ; Medicine ; R
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Kindlin-2 Mediates Mechanical Activation of Cardiac Myofibroblasts

    Elena Godbout / Dong Ok Son / Stephanie Hume / Stellar Boo / Vincent Sarrazy / Sophie Clément / Andras Kapus / Bernhard Wehrle-Haller / Leena Bruckner-Tuderman / Cristina Has / Boris Hinz

    Cells, Vol 9, Iss 2702, p

    2020  Volume 2702

    Abstract: We identify the focal adhesion protein kindlin-2 as player in a novel mechanotransduction pathway that controls profibrotic cardiac fibroblast to myofibroblast activation. Kindlin-2 is co-upregulated with the myofibroblast marker α-smooth muscle actin (α- ...

    Abstract We identify the focal adhesion protein kindlin-2 as player in a novel mechanotransduction pathway that controls profibrotic cardiac fibroblast to myofibroblast activation. Kindlin-2 is co-upregulated with the myofibroblast marker α-smooth muscle actin (α-SMA) in fibrotic rat hearts and in human cardiac fibroblasts exposed to fibrosis-stiff culture substrates and pro-fibrotic TGF-β1. Stressing fibroblasts using ferromagnetic microbeads, stretchable silicone membranes, and cell contraction agonists all result in kindlin-2 translocation to the nucleus. Overexpression of full-length kindlin-2 but not of kindlin-2 missing a putative nuclear localization sequence (∆NLS kindlin-2) results in increased α-SMA promoter activity. Downregulating kindlin-2 with siRNA leads to decreased myofibroblast contraction and reduced α-SMA expression, which is dependent on CC(A/T)-rich GG(CArG) box elements in the α-SMA promoter. Lost myofibroblast features under kindlin-2 knockdown are rescued with wild-type but not ∆NLS kindlin-2, indicating that myofibroblast control by kindlin-2 requires its nuclear translocation. Because kindlin-2 can act as a mechanotransducer regulating the transcription of α-SMA, it is a potential target to interfere with myofibroblast activation in tissue fibrosis.
    Keywords fibrosis ; focal adhesion ; mechanical stress ; nuclear shuttling ; mechanosensation ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome

    Sara Guerrero-Aspizua / Claudio J. Conti / Maria Jose Escamez / Daniele Castiglia / Giovanna Zambruno / Leila Youssefian / Hassan Vahidnezhad / Luis Requena / Peter Itin / Gianluca Tadini / Ivelina Yordanova / Ludovic Martin / Jouni Uitto / Cristina Has / Marcela Del Rio

    Orphanet Journal of Rare Diseases, Vol 14, Iss 1, Pp 1-

    study of a series of 91 patients

    2019  Volume 15

    Abstract: Abstract Background Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin ... ...

    Abstract Abstract Background Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. Results The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. Conclusions This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.
    Keywords Kindler syndrome ; SCC ; Skin cancer ; Bullous disease ; Prevalence ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top