COMP-assisted collagen secretion - a novel intracellular function required for fibrosis

Jan Niklas Schulz, Julian Nüchel, Anja Niehoff, Wilhelm Bloch, Katrin Schönborn, Shujiro Hayashi, Matthias Kamper, Jürgen Brinckmann, Markus Plomann, Mats Paulsson, Thomas Krieg, Frank Zaucke*, Beate Eckes

*Korrespondierende/r Autor/-in für diese Arbeit
12 Zitate (Scopus)

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.
OriginalspracheEnglisch
ZeitschriftJournal of Cell Science
Jahrgang129
Ausgabenummer4
Seiten (von - bis)706-716
Seitenumfang11
ISSN0021-9533
DOIs
PublikationsstatusVeröffentlicht - 01.01.2016

Fingerprint

Untersuchen Sie die Forschungsthemen von „COMP-assisted collagen secretion - a novel intracellular function required for fibrosis“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren