title: Matrin 3 as a key regulator of endothelial cell survival.
abstract: Matrin 3 is an integral component of nuclear matrix architecture that has been implicated in interacting with other nuclear proteins and thus modulating the activity of proximal promoters. In this study, we evaluated the contribution of this protein to proliferation of endothelial cells. To selectively modulate matrin 3 expression, we used siRNA oligonucleotides and transfection of cells with a pEGFP-N1-Mtr3. Our data indicate that downregulation of matrin 3 is responsible for reduced proliferation and leads to necrosis of endothelial cells. This conclusion is supported by observations that reducing matrin 3 expression results in (a) producing signs of necrosis detected by PI staining, LDH release, and scatter parameters in flow cytometry, (b) affecting cell cycle progression. It does not cause (c) membrane asymmetry of cells as indicated by lack of Annexin V binding as well as (d) activation of caspase 3 and cleavage of PARP. We conclude that matrin 3 plays a significant role in controlling cell growth and proliferation, probably via formation of complexes with nuclear proteins that modulate pro- and antiapoptotic signaling pathways. Thus, degradation of matrin 3 may be a switching event that induces a shift from apoptotic to necrotic death of cells.
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Przygodzka
authors.forename: Joanna
authors.initials: J
authors.lastname: Boncela
authors.forename: Czeslaw S
authors.initials: CS
authors.lastname: Cierniewski
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D018613:Microscopy, Confocal; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins