Browsing by Subject "KERATINOCYTES"

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  • Salmenperä, Pertteli; Karhemo, Piia-Riitta; Rasanen, Kati; Laakkonen, Pirjo; Vaheri, Antti (2016)
    Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i.e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-beta-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in softagarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescenceassociated-beta-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. (C) 2016 Elsevier Inc. All rights reserved.
  • Qian, Kui; Pietila, Tuuli; Rönty, Mikko Juhani; Michon, Frederic; Frilander, Mikko J.; Ritari, Jarmo; Tarkkanen, Jussi; Paulin, Lars; Auvinen, Petri; Auvinen, Eeva (2013)
  • Tervaniemi, Mari H.; Katayama, Shintaro; Skoog, Tiina; Siitonen, H. Annika; Vuola, Jyrki; Nuutila, Kristo; Tammimies, Kristiina; Suomela, Sari; Kankuri, Esko; Kere, Juha; Elomaa, Outi (2018)
    Background: CCHCR1 (Coiled Coil alpha-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centiosomal piotein, as well as a component of cytoplasmic piocessmg bodies (P-bodies) that regulate mRNA turnovel. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings, it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants. Results: The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though seveial similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies. Conclusions: CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and division. The piesent findings may explain the previous inconsistent obseivations about the functions of CCHCR1.
  • Tayem, Raneem; Niemann, Catherin; Pesch, Monika; Morgner, Jessica; Niessen, Carien M.; Wickström, Sara A.; Aumailley, Monique (2021)
    The skin epidermis is attached to the underlying dermis by a laminin 332 (Lm332)-rich basement membrane. Consequently, loss of Lm332 leads to the severe blistering disorder epidermolysis bullosa junctionalis in humans and animals. Owing to the indispensable role of Lm332 in keratinocyte adhesion in vivo, the severity of the disease has limited research into other functions of the protein. We have conditionally disrupted Lm332 expression in basal keratinocytes of adult mice. Although blisters develop along the interfollicular epidermis, hair follicle basal cells provide sufficient anchorage of the epidermis to the dermis, making inducible deletion of the Lama3 gene compatible with life. Loss of Lm332 promoted the thickening of the epidermis and exaggerated desquamation. Global RNA expression analysis revealed major changes in the expression of keratins, cornified envelope proteins, and cellular stress markers. These modifications of the keratinocyte genetic program are accompanied by changes in cell shape and disorganization of the actin cytoskeleton. These data indicate that loss of Lm332-mediated progenitor cell adhesion alters cell fate and disturbs epidermal homeostasis.
  • Fyhrquist, Nanna; Muirhead, Gareth; Prast-Nielsen, Stefanie; Jeanmougin, Marine; Olah, Peter; Skoog, Tiina; Jules-Clement, Gerome; Feld, Micha; Barrientos-Somarribas, Mauricio; Sinkko, Hanna; van den Bogaard, Ellen H.; Zeeuwen, Patrick L. J. M.; Rikken, Gijs; Schalkwijk, Joost; Niehues, Hanna; Däubener, Walter; Eller, Silvia Kathrin; Alexander, Helen; Pennino, Davide; Suomela, Sari; Tessas, Ioannis; Lybeck, Emilia; Baran, Anna M.; Darban, Hamid; Gangwar, Roopesh Singh; Gerstel, Ulrich; Jahn, Katharina; Karisola, Piia; Yan, Lee; Hansmann, Britta; Katayama, Shintaro; Meller, Stephan; Bylesjo, Max; Hupe, Philippe; Levi-Schaffer, Francesca; Greco, Dario; Ranki, Annamari; Schröder, Jens M.; Barker, Jonathan; Kere, Juha; Tsoka, Sophia; Lauerma, Antti; Soumelis, Vassili; Nestle, Frank O.; Homey, Bernhard; Andersson, Björn; Alenius, Harri (2019)
    Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
  • Ala-Houhala, Meri J.; Karppinen, Toni; Vahavihu, Katja; Kautiainen, Hannu; Dombrowski, Yvonne; Snellman, Erna; Schauber, Juergen; Reunala, Timo (2014)
  • Moilanen, Jyri M.; Loeffek, Stefanie; Kokkonen, Nina; Salo, Sirpa; Vayrynen, Juha P.; Hurskainen, Tiina; Manninen, Aki; Riihila, Pilvi; Heljasvaara, Ritva; Franzke, Claus-Werner; Kahari, Veli-Matti; Salo, Tuula; Makinen, Markus J.; Tasanen, Kaisa (2017)
    Collagen XVII and integrin alpha 6 beta 4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin alpha 6 beta 4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin.2, collagen XVII and integrin beta 4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen's disease. The expression of laminin.2 was highest in SCC samples, whereas the expression of collagen XVII and integrin beta 4 varied greatly in SCC and its precursors. Collagen XVII and integrin beta 4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin beta 4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin beta 4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin beta 4 contribute to SCC tumorigenesis.
  • Gao, Yuge; Yao, Xinyu; Zhai, Yumeng; Li, Li; Li, Huini; Sun, Xianqi; Yu, Pei; Xue, Tiankuo; Li, Yuzhen; Hu, Yizhou (2021)
    Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.