HtrA1 (high-temperature requirement protein A1) is a secreted multidomain protein with proven serine protease activity and the ability to regulate TGF-β (transforming growth factor-β)/BMP (bone morphogenetic protein) signalling. There is increasing evidence that HtrA1 regulates several pathological processes, including tumour development, Alzheimer's disease, age-related macular degeneration and osteoarthritis, although the mechanism(s) by which it regulates these processes have not been fully elucidated. Using overexpression and knock-down strategies, we have evidence demonstrating that HtrA1 is also a key regulator of physiological and pathological matrix mineralization in vitro. We propose that HtrA1 regulates mineralization by inhibiting TGF-β/BMP signalling and/or by cleaving specific matrix proteins, including decorin and MGP (matrix Gla protein). Taken together, these studies suggest that HtrA1 may be a novel therapeutic target for several diseases.
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August 2007
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Conference Article|
July 20 2007
HtrA1: a novel regulator of physiological and pathological matrix mineralization?
A.E. Canfield;
A.E. Canfield
1
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (email ann.canfield@manchester.ac.uk).
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K.D. Hadfield;
K.D. Hadfield
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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C.F. Rock;
C.F. Rock
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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E.C. Wylie;
E.C. Wylie
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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F.L. Wilkinson
F.L. Wilkinson
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
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Publisher: Portland Press Ltd
Received:
April 01 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 669–671.
Article history
Received:
April 01 2007
Citation
A.E. Canfield, K.D. Hadfield, C.F. Rock, E.C. Wylie, F.L. Wilkinson; HtrA1: a novel regulator of physiological and pathological matrix mineralization?. Biochem Soc Trans 1 August 2007; 35 (4): 669–671. doi: https://doi.org/10.1042/BST0350669
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