title: UAP56 is an important mediator of angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation.
abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reported that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.
authors.affiliation: Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Abha
authors.initials: A
authors.lastname: Sahni
authors.forename: Nadan
authors.initials: N
authors.lastname: Wang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Alexis
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D050684:E2F Transcription Factors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D050684:E2F Transcription Factors; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D000804:Angiotensin II; D004247:DNA; C518885:Ddx39b protein, mouse; C075446:Ddx39b protein, rat; D053487:DEAD-box RNA Helicases