title: COMP-assisted collagen secretion--a novel intracellular function required for fibrosis.
abstract: Cartilage oligomeric matrix protein (COMP) is an abundant component in the extracellular matrix (ECM) of load-bearing tissues such as tendons and cartilage. It provides adaptor functions by bridging different ECM structures. We have previously shown that COMP is also a constitutive component of healthy human skin and is strongly induced in fibrosis. It binds directly and with high affinity to collagen I and to collagen XII that decorates the surface of collagen I fibrils. We demonstrate here that lack of COMP-collagen interaction in the extracellular space leads to changes in collagen fibril morphology and density, resulting in altered skin biomechanical properties. Surprisingly, COMP also fulfills an important intracellular function in assisting efficient secretion of collagens, which were retained in the endoplasmic reticulum of COMP-null fibroblasts. Accordingly, COMP-null mice showed severely attenuated fibrotic responses in skin. Collagen secretion was fully restored by introducing wild-type COMP. Hence, our work unravels a new, non-structural and intracellular function of the ECM protein COMP in controlling collagen secretion.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Jan-Niklas
authors.initials: JN
authors.lastname: Schulz
authors.affiliation: Center for Biochemistry, University of Cologne, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Nüchel
authors.affiliation: Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, Cologne, Germany German Sport University, Cologne, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Niehoff
authors.affiliation: German Sport University, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schönborn
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Center for Biochemistry, University of Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kamper
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany Institute of Virology and Cell Biology, University of Lübeck, Lübeck, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brinckmann
authors.affiliation: Center for Biochemistry, University of Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Plomann
authors.affiliation: Center for Biochemistry, University of Cologne, Germany Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, Cologne, Germany Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Center for Biochemistry, University of Cologne, Germany Cologne Center for Musculoskeletal Biomechanics (CCMB), University of Cologne, Cologne, Germany frank.zaucke@uni-koeln.de beate.eckes@uni-koeln.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Zaucke
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany frank.zaucke@uni-koeln.de beate.eckes@uni-koeln.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
mesh_terms: D000818:Animals; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D008810:Mice, Inbred C57BL; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D024022:Fibrillar Collagens
keywords: COMP; Collagen; Extracellular matrix; Fibrosis; Secretion