HtrA1: a novel regulator of physiological and pathological matrix mineralization?
HtrA1 (high-temperature requirement protein A1) is a secreted multidomain protein with proven serine protease activity and the ability to regulate TGF-beta (transforming growth factor-beta)/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-beta/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.
Canfield
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Wellcome Trust Centre for Cell-Matrix Research, Faculty of Medical and Human Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. ann.canfield@manchester.ac.uk
Hadfield
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KD
Rock
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Wylie
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Wilkinson
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D000818:Animals; D018407:Bacterial Physiological Phenomena; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D012697:Serine Endopeptidases / Q000502:physiology*
D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases