title: Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control.
abstract: It has long been known that Tissue Factor (TF) plays a role in blood coagulation and has a direct thrombotic action that is closely related to cardiovascular risk, but it is becoming increasingly clear that it has a much wider range of biological functions that range from inflammation to immunity. It is also involved in maintaining heart haemostasis and structure, and the observation that it is down-regulated in the myocardium of patients with dilated cardiomyopathy suggests that it influences cell-to-cell contact stability and contractility, and thus contributes to cardiac dysfunction. However, the molecular mechanisms underlying these coagulation-independent functions have not yet been fully elucidated. In order to analyse the influence of TF on the cardiomyocitic proteome, we used functional biochemical approaches incorporating label-free quantitative proteomics and gene silencing, and found that this provided a powerful means of identifying a new role for TF in regulating splicing machinery together with the expression of several proteins of the spliceosome, and mRNA metabolism with a considerable impact on cell viability.
  
  
  CONCLUSIONS
  In this study, using quantitative proteomics and functional biochemical approaches, we define for the first time that, in addition to its primary role in blood coagulation, Tissue Factor also plays a novel role in regulating cell splicing machinery, with a relevant impact on cell survival. This new function may help to explain the wide range of biological activities of TF, and thus provide fruitful clues for developing new strategies for treating human diseases in which TF is dysregulated.
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy.
authors: Sabrina
authors: S
authors: Lento
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy.
authors: Maura
authors: M
authors: Brioschi
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy.
authors: Simona
authors: S
authors: Barcella
authors: National Institute for Health Research Comprehensive Biomedical Research Centre, King's College London, UK; Department of Medical and Molecular Genetics, King's College London, UK; Bradford School of Pharmacy, School of Life Sciences, University of Bradford, UK.
authors: Md Talat
authors: MT
authors: Nasim
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy.
authors: Stefania
authors: S
authors: Ghilardi
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy.
authors: Silvia Stella
authors: SS
authors: Barbieri
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
authors: Elena
authors: E
authors: Tremoli
authors: Centro Cardiologico Monzino IRCCS, Milano, Italy. Electronic address: cristina.banfi@ccfm.it.
authors: Cristina
authors: C
authors: Banfi
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D012326:RNA Splicing; D013925:Thromboplastin / Q000096:biosynthesis*
chemical_list: D013925:Thromboplastin
keywords: Cardiomyocytic cells; Label-free quantitative mass spectrometry; Proteomics; Spliceosome; Splicing; Tissue factor