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Processing of procollagen III by meprins: new players in extracellular matrix assembly?
Daniel Kronenberg1, Bernd C Bruns, Catherine Moali
1Institut de Biologie et Chimie des Protéines, CNRS/Université de Lyon UMR 5086, IFR 128 Biosciences Gerland-Lyon Sud, Lyon, France.
Abstract:
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.
Insights
Meprins alpha and beta process procollagen III, aiding collagen fibril formation. These metalloproteinases are more efficient than BMP-1 and show altered activity with PCPE-1, suggesting roles in tissue remodeling.
Area of Science:
- Biochemistry
- Cell Biology
- Dermatology
Background:
- Meprins alpha and beta are zinc metalloproteinases involved in extracellular matrix remodeling.
- Their role in procollagen processing, a key step in collagen fibril formation, was previously unknown.
Purpose of the Study:
- To investigate the novel function of meprins alpha and beta in the proteolytic processing of procollagens.
- To compare the activity of meprins with known procollagen C-proteinases like BMP-1.
Main Methods:
- Enzymatic assays to assess meprin activity on procollagen III.
- Comparison of cleavage sites with BMP-1 and tolloid proteinase family members.
- Analysis of meprin expression in human skin cells and fibrotic tissue.
Main Results:
- Both meprins alpha and beta efficiently release N- and C-propeptides from procollagen III.
- Meprins cleave procollagen III at the same site as BMP-1, but more effectively.
- PCPE-1 inhibits meprin activity on procollagen III, unlike its stimulatory effect on BMP-1.
- Meprin alpha is expressed in dermal fibroblasts, with increased levels in keloids; meprin beta is also detected in fibrotic skin.
Conclusions:
- Meprins play a significant role in the matrix assembly of collagen III by processing procollagens.
- Their distinct regulation by PCPE-1 and potent activity suggest specialized functions in collagen deposition.
- Increased meprin expression in fibrotic skin indicates a potential role in pathological collagen remodeling.
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