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Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis.
Beckmann, Denise; Römer-Hillmann, Anja; Krause, Annika; Hansen, Uwe; Wehmeyer, Corinna; Intemann, Johanna; de Gorter, David J J; Dankbar, Berno; Hillen, Jan; Heitzmann, Marianne; Begemann, Isabell; Galic, Milos; Weinhage, Toni; Foell, Dirk; Ai, Rizi; Kremerskothen, Joachim; Kiener, Hans P; Müller, Sylvia; Kamradt, Thomas; Schröder, Christopher; Leitão, Elsa; Horsthemke, Bernhard; Rosenstiel, Philip; Nordström, Karl; Gasparoni, Gilles; Gasparoni, Nina; Walter, Jörn; Li, Na; Yang, Xinyi; Chung, Ho-Ryun; Pavenstädt, Hermann; Lindemann, Nico; Schnittler, Hans J; Wang, Wei; Firestein, Gary S; Pap, Thomas; Korb-Pap, Adelheid.
Affiliation
  • Beckmann D; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Römer-Hillmann A; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Krause A; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Hansen U; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Wehmeyer C; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Intemann J; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • de Gorter DJJ; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Dankbar B; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Hillen J; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Heitzmann M; Institute of Musculoskeletal Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D3, Münster, Germany.
  • Begemann I; Institute of Medical Physics and Biophysics, University of Münster, Robert-Koch Straße 31, Münster, Germany.
  • Galic M; Institute of Medical Physics and Biophysics, University of Münster, Robert-Koch Straße 31, Münster, Germany.
  • Weinhage T; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Domagkstraße 3, Münster, Germany.
  • Foell D; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Domagkstraße 3, Münster, Germany.
  • Ai R; Department of Chemistry and Biochemistry, 9500 Gilman Drive, UC San Diego, La Jolla, CA, USA.
  • Kremerskothen J; Department of Nephrology and Rheumatology, Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, Germany.
  • Kiener HP; Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
  • Müller S; Institute for Immunology, Jena University Hospital, Friedrich Schiller University, Jena, Leutragraben 3, Jena, Germany.
  • Kamradt T; Institute for Immunology, Jena University Hospital, Friedrich Schiller University, Jena, Leutragraben 3, Jena, Germany.
  • Schröder C; Genome Informatics, Institute of Human Genetics, University of Duisburg-Essen, Virchowstraße 183, Essen, Germany.
  • Leitão E; Institute of Human Genetics, University Hospital of Essen, University of Duisburg-Essen, Hufelandstraße 55, Essen, Germany.
  • Horsthemke B; Institute of Human Genetics, University Hospital of Essen, University of Duisburg-Essen, Hufelandstraße 55, Essen, Germany.
  • Rosenstiel P; Institute of Clinical Molecular Biology, University of Kiel, Rosalind-Franklin-Straße 12, Kiel, Germany.
  • Nordström K; Department of Genetics/Epigenetics, Saarland University, Campus Saarbrücken, Building A2 4, Saarbrücken, Germany.
  • Gasparoni G; Department of Genetics/Epigenetics, Saarland University, Campus Saarbrücken, Building A2 4, Saarbrücken, Germany.
  • Gasparoni N; Department of Genetics/Epigenetics, Saarland University, Campus Saarbrücken, Building A2 4, Saarbrücken, Germany.
  • Walter J; Department of Genetics/Epigenetics, Saarland University, Campus Saarbrücken, Building A2 4, Saarbrücken, Germany.
  • Li N; Max Planck Institute for Molecular Genetics, Otto-Warburg-Laboratories, Epigenomics, Ihnestraße 63-73, Berlin, Germany.
  • Yang X; Max Planck Institute for Molecular Genetics, Otto-Warburg-Laboratories, Epigenomics, Ihnestraße 63-73, Berlin, Germany.
  • Chung HR; Max Planck Institute for Molecular Genetics, Otto-Warburg-Laboratories, Epigenomics, Ihnestraße 63-73, Berlin, Germany.
  • Pavenstädt H; Institute of Medical Bioinformatics and Biostatistics, Philipps-University Marburg, Bunsenstraße 3, Marburg, Germany.
  • Lindemann N; Department of Nephrology and Rheumatology, Internal Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, Germany.
  • Schnittler HJ; Institute of Anatomy and Vascular Biology, University of Münster, Vesaliusweg 2-4, Münster, Germany.
  • Wang W; Institute of Anatomy and Vascular Biology, University of Münster, Vesaliusweg 2-4, Münster, Germany.
  • Firestein GS; Department of Chemistry and Biochemistry, 9500 Gilman Drive, UC San Diego, La Jolla, CA, USA.
  • Pap T; Department of Cellular and Molecular Medicine, 9500 Gilman Drive, UCSD School of Medicine, La Jolla, CA, USA.
  • Korb-Pap A; Division of Rheumatology, Allergy and Immunology, 9500 Gilman Drive, UCSD School of Medicine, La Jolla, CA, USA.
Nat Commun ; 12(1): 3624, 2021 06 15.
Article in En | MEDLINE | ID: mdl-34131132
The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/ß-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.
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Full text: 1 Database: MEDLINE Main subject: Arthritis / Cell Transformation, Neoplastic / Adherens Junctions / Cytoskeletal Proteins / Adaptor Proteins, Signal Transducing / LIM Domain Proteins / Fibroblasts Type of study: Prognostic_studies Limits: Animals Language: En Year: 2021 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Arthritis / Cell Transformation, Neoplastic / Adherens Junctions / Cytoskeletal Proteins / Adaptor Proteins, Signal Transducing / LIM Domain Proteins / Fibroblasts Type of study: Prognostic_studies Limits: Animals Language: En Year: 2021 Type: Article