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  1. Article ; Online: Potential Role of AGR2 for Mammalian Skin Wound Healing.

    Kosykh, Anastasiya V / Tereshina, Maria B / Gurskaya, Nadya G

    International journal of molecular sciences

    2023  Volume 24, Issue 9

    Abstract: The limited ability of mammals to regenerate has garnered significant attention, particularly in regard to skin wound healing (WH), which is a critical step for regeneration. In human adults, skin WH results in the formation of scars following injury or ... ...

    Abstract The limited ability of mammals to regenerate has garnered significant attention, particularly in regard to skin wound healing (WH), which is a critical step for regeneration. In human adults, skin WH results in the formation of scars following injury or trauma, regardless of severity. This differs significantly from the scarless WH observed in the fetal skin of mammals or anamniotes. This review investigates the role of molecular players involved in scarless WH, which are lost or repressed in adult mammalian WH systems. Specifically, we analyze the physiological role of Anterior Gradient (AGR) family proteins at different stages of the WH regulatory network. AGR is activated in the regeneration of lower vertebrates at the stage of wound closure and, accordingly, is important for WH. Mammalian AGR2 is expressed during scarless WH in embryonic skin, while in adults, the activity of this gene is normally inhibited and is observed only in the mucous epithelium of the digestive tract, which is capable of full regeneration. The combination of AGR2 unique potencies in postnatal mammals makes it possible to consider it as a promising candidate for enhancing WH processes.
    MeSH term(s) Animals ; Humans ; Wound Healing/physiology ; Cicatrix/pathology ; Skin/pathology ; Mammals ; Epithelium/pathology ; Mucoproteins/genetics ; Oncogene Proteins/genetics
    Chemical Substances AGR2 protein, human ; Mucoproteins ; Oncogene Proteins
    Language English
    Publishing date 2023-04-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24097895
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: EBS in Children with De Novo Pathogenic Variants Disturbing

    Kosykh, Anastasiya V / Ryumina, Irina I / Botkina, Alexandra S / Evtushenko, Nadezhda A / Zhigmitova, Elena B / Martynova, Aleksandra A / Gurskaya, Nadya G / Rebrikov, Denis V

    International journal of molecular sciences

    2024  Volume 25, Issue 5

    Abstract: Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents ...

    Abstract Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the
    MeSH term(s) Child ; Infant, Newborn ; Humans ; Child, Preschool ; Epidermolysis Bullosa Simplex/genetics ; Mutation ; Phenotype ; Keratins/genetics ; Epidermis/pathology ; Keratin-5/genetics
    Chemical Substances Keratins (68238-35-7) ; Keratin-5
    Language English
    Publishing date 2024-03-04
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25052989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex.

    Evtushenko, Nadezhda A / Beilin, Arkadii K / Kosykh, Anastasiya V / Vorotelyak, Ekaterina A / Gurskaya, Nadya G

    International journal of molecular sciences

    2021  Volume 22, Issue 22

    Abstract: Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the ... ...

    Abstract Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes. Keratin aggregates display impaired dynamics of assembly and diminished solubility and appear to be the trigger for endoplasmic reticulum (ER) stress upon being phosphorylated by MAPKs. Global changes in cellular signaling mainly occur in cases of severe dominant EBS mutations. The spectrum of changes initiated by phosphorylation includes the inhibition of proteasome degradation, TNF-α signaling activation, deregulated proliferation, abnormal cell migration, and impaired adherence of keratinocytes. ER stress also leads to the release of proinflammatory danger-associated molecular pattern (DAMP) molecules, which enhance avalanche-like inflammation. Many instances of positive feedback in the course of cellular stress and the development of sterile inflammation led to systemic chronic inflammation in EBS. This highlights the role of keratin in the maintenance of epidermal and immune homeostasis.
    MeSH term(s) Alarmins/genetics ; Alarmins/metabolism ; Endoplasmic Reticulum Stress/genetics ; Epidermis/metabolism ; Epidermis/pathology ; Epidermolysis Bullosa Simplex/genetics ; Epidermolysis Bullosa Simplex/metabolism ; Epidermolysis Bullosa Simplex/pathology ; Gene Expression Regulation ; Humans ; Inflammation ; Intermediate Filaments/metabolism ; Intermediate Filaments/pathology ; Intermediate Filaments/ultrastructure ; Keratin-14/genetics ; Keratin-14/metabolism ; Keratin-5/genetics ; Keratin-5/metabolism ; Keratinocytes/metabolism ; Keratinocytes/pathology ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Proteasome Endopeptidase Complex/metabolism ; Protein Aggregates ; Proteolysis ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Alarmins ; KRT14 protein, human ; KRT5 protein, human ; Keratin-14 ; Keratin-5 ; Protein Aggregates ; Tumor Necrosis Factor-alpha ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222212446
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation.

    Cherkashina, Olga L / Morgun, Elena I / Rippa, Alexandra L / Kosykh, Anastasiya V / Alekhnovich, Alexander V / Stoliarzh, Aleksey B / Terskikh, Vasiliy V / Vorotelyak, Ekaterina A / Kalabusheva, Ekaterina P

    International journal of molecular sciences

    2023  Volume 24, Issue 16

    Abstract: Most of the knowledge about human skin homeostasis, development, wound healing, and diseases has been accumulated from human skin biopsy analysis by transferring from animal models and using different culture systems. Human-to-mouse xenografting is one ... ...

    Abstract Most of the knowledge about human skin homeostasis, development, wound healing, and diseases has been accumulated from human skin biopsy analysis by transferring from animal models and using different culture systems. Human-to-mouse xenografting is one of the fundamental approaches that allows the skin to be studied in vivo and evaluate the ongoing physiological processes in real time. Humanized animals permit the actual techniques for tracing cell fate, clonal analysis, genetic modifications, and drug discovery that could never be employed in humans. This review recapitulates the novel facts about mouse skin self-renewing, regeneration, and pathology, raises issues regarding the gaps in our understanding of the same options in human skin, and postulates the challenges for human skin xenografting.
    MeSH term(s) Humans ; Animals ; Mice ; Transplantation, Heterologous ; Skin ; Heterografts ; Wound Healing ; Biopsy
    Language English
    Publishing date 2023-08-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241612769
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: hTERT-Driven Immortalization of RDEB Fibroblast and Keratinocyte Cell Lines Followed by Cre-Mediated Transgene Elimination.

    Evtushenko, Nadezhda A / Beilin, Arkadii K / Dashinimaev, Erdem B / Ziganshin, Rustam H / Kosykh, Anastasiya V / Perfilov, Maxim M / Rippa, Alexandra L / Alpeeva, Elena V / Vasiliev, Andrey V / Vorotelyak, Ekaterina A / Gurskaya, Nadya G

    International journal of molecular sciences

    2021  Volume 22, Issue 8

    Abstract: The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we ... ...

    Abstract The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we developed expansible cultures of RDEB fibroblasts and keratinocytes. We showed that they display the properties of their founders, including morphology, contraction ability and expression of the respective specific markers including reduced secretion of type VII collagen (C7). The immortalized keratinocytes retained normal stratification in 3D skin equivalents. The comparison of secreted protein patterns from immortalized RDEB and healthy keratinocytes revealed the differences in the contents of the extracellular matrix that were earlier observed specifically for RDEB. We demonstrated the possibility to reverse the genotype of immortalized cells to the state closer to the progenitors by the Cre-dependent hTERT switch off. Increased β-galactosidase activity and reduced proliferation of fibroblasts were shown after splitting out of transgenes. We anticipate our cell lines to be tractable models for studying RDEB from the level of single-cell changes to the evaluation of 3D skin equivalents. Our approach permits the creation of standardized and expandable models of RDEB that can be compared with the models based on primary cell cultures.
    MeSH term(s) Adolescent ; Adult ; Biomarkers ; Cell Line, Transformed ; Cell Proliferation ; Cellular Senescence/genetics ; Child ; Epidermolysis Bullosa Dystrophica/etiology ; Epidermolysis Bullosa Dystrophica/metabolism ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Fluorescent Antibody Technique ; Gene Knockdown Techniques ; Gene Order ; Genetic Vectors/genetics ; Homologous Recombination ; Humans ; Immunohistochemistry ; Integrases/metabolism ; Keratinocytes/metabolism ; Male ; Middle Aged ; Mutation ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 1/metabolism ; Primary Cell Culture ; Proteomics/methods ; Telomerase/genetics ; Telomerase/metabolism ; Transgenes ; Young Adult
    Chemical Substances BMI1 protein, human ; Biomarkers ; Polycomb Repressive Complex 1 (EC 2.3.2.27) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-) ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2021-04-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22083809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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