Matrix gla protein is regulated by a mechanism functionally related to the calcium-sensing receptor.
Matrix Gla protein (MGP) is a mineral binding extra-cellular matrix protein which is thought to be a key inhibitor of tissue and vascular calcification. It is known to be upregulated in areas of extracellular calcification possibly to limit further harmful calcification. In this study we have demonstrated that extracellular ionic calcium (high levels of which induce calcification) is a key signal for MGP regulation and that this effect is mediated by a G protein mediated cation-sensing mechanism, functionally related to, but molecularly distinct from the calcium-sensing receptor. We therefore propose that this novel cation sensing mechanism may play a homeostatic role in preventing pathological calcification.
Farzaneh-Far
A
A
Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI level 6, Hills Road, Cambridge, CB2 2QQ, United Kingdom. aff24@cam.ac.uk
Proudfoot
D
D
Weissberg
P L
PL
Shanahan
C M
CM
D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000819:agonists / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D002412:Cations; D016326:Extracellular Matrix Proteins; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D000097568:Matrix Gla Protein; C473605:extracellular calcium cation-sensing receptor, rat