Transcriptional regulation of matrix gla protein

Farzaneh‐Far, Afshin; Weissberg, Peter L.; Proudfoot, Diane; Shanahan, Catherine M.

doi:10.1007/s003920170040

Cited by 36 publications

(35 citation statements)

References 36 publications

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“…C/EBP and retinoic acid response elements exist immediately downstream and an ETS site immediately upstream of the TϪ138C polymorphism. We have confirmed that the MGP promoter is repressed by retinoic acid as shown by others (28) and that the polymorphism has no effect on this response (29). The transcription factor C/EBP␤ has previously been shown to be a strong stimulator of MGP transcription acting through the Ϫ138 to Ϫ102 region of the promoter (28).…”

Section: Fig 13supporting

confidence: 67%

A Polymorphism of the Human Matrix γ-Carboxyglutamic Acid Protein Promoter Alters Binding of an Activating Protein-1 Complex and Is Associated with Altered Transcription and Serum Levels

Farzaneh‐Far¹,

Davies²,

Braam³

et al. 2001

Journal of Biological Chemistry

107

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Matrix ␥-carboxyglutamic acid protein (MGP) is a mineral-binding extracellular matrix protein synthesized by vascular smooth muscle cells (VSMCs) and chondrocytes that is thought to be a key regulator of tissue calcification. In this study, we identified four polymorphisms in the promoter region of the human MGP gene. Transfection studies showed that the G؊7A and T؊138C polymorphisms have an important impact on in vitro promoter activity when transiently transfected into VSMCs. We found that one of these polymorphisms (T؊138C) is significantly correlated with serum MGP levels in human subjects. Promoter deletion analysis showed that this polymorphism lies in a region of the promoter critical for transcription in VSMCs. This region contains a potential activating protein-1 (AP-1) binding element located between ؊142 and ؊136. We have demonstrated that the T؊138C polymorphism results in altered binding of an AP-1 complex to this region. The ؊138T allelic variant binds AP-1 complexes consisting primarily of c-Jun, JunB and its partners Fra-1 and Fra-2 in rat VSMC. Furthermore, the ؊138T variant form of the promoter was induced following phorbol 12-myristate 13-acetate treatment, while the ؊138C variant was refractive to phorbol 12-myristate 13-acetate treatment, confirming that AP-1 factors preferentially bind to the ؊138T variant. This study therefore suggests that a common polymorphism of the MGP promoter influences binding of the AP-1 complex, which may lead to altered transcription and serum levels. This could have important implications for diseases such as atherosclerosis and aortic valve stenosis, since it strongly suggests a genetic basis for regulation of tissue calcification.

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Section: Fig 13supporting

confidence: 67%

A Polymorphism of the Human Matrix γ-Carboxyglutamic Acid Protein Promoter Alters Binding of an Activating Protein-1 Complex and Is Associated with Altered Transcription and Serum Levels

Farzaneh‐Far¹,

Davies²,

Braam³

et al. 2001

Journal of Biological Chemistry

107

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“…10 Apatite biofilms in the heart are likely to change shear forces in the blood, and contribute in this way to nonspecific circulatory problems. 11,12 A closer inspection of the SEM images showing NB in the heart of humans 4,5 strongly supports this picture. NB appear to possess at least three qualities, which may cause alone or cooperatively harm to living systems.…”

supporting

confidence: 75%

Superadhesion: Attachment of Nanobacteria to Tissues − Model Simulation

Sommer

Çehreli

Akça

et al. 2004

Crystal Growth & Design

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Adhesion is common in the bacterial world and is partially mediated by slime. Nanobacteria (NB) seem to attach by slime as well as by the protecting nanocrystalline apatite shell, securing their survival in hostile milieus. Identification of NB in the human heart has brought the particles into the focus of material scientists. In view of the size distribution of the apatite nanovesicles (80-300 nm), simulation of their interaction with tissues can be performed via nanosuspensions and mirror-polished titanium substrates. Due to its wide biocompatibility, titanium is an ideal body tissue substitute. Here we show in a model simulation that the apatite nanovesicles are likely to perform also an anchoring function, specific to the mineral apatite. Anchoring may prevent solitary NB from elimination from the body, and enforce existing toxic potentials. The capacity of the apatite nanoparticles to bind to tissues in aqueous liquids, and the pronounced tendency of NB to form mineralized biofilms, indicate that NB could affect intracardiac fluid forces. Adhesion and protection represent a unique combination, which may stimulate the design of novel drug release systems based on apatite nanovesicles.

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“…14 arterial stiffening) [44]. Another focus for potential synergy between vitamin K and vitamin D represents the above mentioned morphogenic protein Bnp-2, the expression of which is regulated by both MGP and calcitriol [39,45].…”

Section: Accepted Manuscriptmentioning

confidence: 99%