Processing of procollagen III by meprins: new players in extracellular matrix assembly?
Meprins α and β, a subgroup of zinc metalloproteinases belonging to the astacin family, are known to cleave components of the extracellular matrix, either during physiological remodeling or in pathological situations. In this study we present a new role for meprins in matrix assembly, namely the proteolytic processing of procollagens. Both meprins α and β release the N- and C-propeptides from procollagen III, with such processing events being critical steps in collagen fibril formation. In addition, both meprins cleave procollagen III at exactly the same site as the procollagen C-proteinases, including bone morphogenetic protein-1 (BMP-1) and other members of the tolloid proteinase family. Indeed, cleavage of procollagen III by meprins is more efficient than by BMP-1. In addition, unlike BMP-1, whose activity is stimulated by procollagen C-proteinase enhancer proteins (PCPEs), the activity of meprins on procollagen III is diminished by PCPE-1. Finally, following our earlier observations of meprin expression by human epidermal keratinocytes, meprin α is also shown to be expressed by human dermal fibroblasts. In the dermis of fibrotic skin (keloids), expression of meprin α increases and meprin β begins to be detected. Our study suggests that meprins could be important players in several remodeling processes involving collagen fiber deposition.
Kronenberg
Daniel
D
Institut de Biologie et Chimie des Protéines, CNRS/Université de Lyon UMR 5086, IFR 128 Biosciences Gerland-Lyon Sud, Lyon, France.
Bruns
Bernd C
BC
Moali
Catherine
C
Vadon-Le Goff
Sandrine
S
Sterchi
Erwin E
EE
Traupe
Heiko
H
Böhm
Markus
M
Hulmes
David J S
DJ
Stöcker
Walter
W
Becker-Pauly
Christoph
C
D055395:Bone Morphogenetic Protein 1 / Q000378:metabolism; D002478:Cells, Cultured; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005355:Fibrosis; D057809:HEK293 Cells; D006801:Humans; D007627:Keloid / Q000473:pathology* / Q000503:physiopathology; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D008666:Metalloendopeptidases; C053833:meprin A; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1