Campus Stem Cell Lab meeting, today, Tuesday, April 23
Sue Gilbert
Our next talk this semester will be on Tuesday, April 23, and will start at noon promptly. We will continue to meet in The Wisconsin Institutes of Discovery (WID) for most of the talks. We will be meeting in the H.F. Deluca Forum in the Town Center on the first floor. Please ask at Information Desk if you are unsure where to go. We will continue to provide sandwiches and chips starting at 11:50am (water will be provided but if you want something else to drink please bring your own.)
Date: Tuesday, April 23
Speaker: Daniel DiRenzo, Postdoctoral Trainee (Kent Lab), Vascular Surgery
Title: TGF-beta/SMAD3 Driven Smooth Muscle Cell De-differentiation
Abstract: Approximately 15.8 million people in the USA are diagnosed with coronary artery disease due to the development of a fatty plaque in the artery termed atherosclerosis. Current methods to treat atherosclerosis are initially effective but vessel re-narrowing (restenosis) occurs in approximately 25-50% of balloon angioplasty patients and up to 15% of patients with drug-eluting stents. Restenosis occurs due to the proliferation and migration of arterial smooth muscle cells (SMCs) that contribute to a dense, cellular plaque in the vessel lumen where the fatty atherosclerotic plaque had previously formed. SMCs acquire the capacity to contribute to neointimal hyperplasia through a de-differentiation process that includes downregulation of their contractile gene expression and conversion to a phenotype that includes proliferation, migration, and matrix synthesis.
Expression of TGFβ and its downstream signaling protein, Smad3, are greatly upregulated following vascular injury, including balloon angioplasty. Interestingly, Smad3 overexpressing SMCs show enhanced proliferation and migration and overexpression of Smad3 in rat carotid arteries enhances neo-intimal hyperplasia following balloon angioplasty. These results lead us to hypothesize that TGFβ signaling, in the context of upregulated Smad3, drives SMC de-differentiation leading to enhanced cellular proliferation and migration.
We utilized primary rat SMCs infected with adenovirus constructs overexpressing Smad3 or GFP control and performed gene expression microarrays followed by GO term analysis which revealed that genes involved in embryonic tissue development and stem/progenitor cell differentiation were significantly enriched in TGFβ/Smad3 stimulated cells. Confirmatory qRT-PCR demonstrated that the contractile genes SM-MHC, smooth muscle actin, and calponin were significantly downregulated whereas stem/progenitor gene expression was upregulated. These results strongly suggest that TGFβ/Smad3 stimulation is a powerful de-differentiation signal in SMCs and plays an important role in the development of neo-intimal hyperplasia.
Reminder: If you are talking this Seminar Series for credit, please check in with Sue Gilbert at the back of the room.
Next talk: On Tuesday, April 30, our speaker will be Daryl Nelson, Graduate Fellow, Cell and Regenerative Biology (Lyons lab), who will be speaking on “The Homeobox Transcription Factor, Irx4, Identifies a Mutipotent, Ventricular-specific Cardiac Progenitor”. This talk will be in 1360 Biotechnology Center (Note: Change of venue) 425 Henry Mall, and will include pizza.
A list of the talks for the semester is found at:
http://stemcells.wisc.edu/node/246
Thank you for supporting this venue for the sharing of information.
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Sue Gilbert
Office Operations Associate
Stem Cell and Regenerative Medicine Center
5036 WIMR
1111 Highland Avenue
Madison, WI 53705-2275
Tel: (608) 263-2982
FAX: (608) 263-5267
"The science fiction of yesterday happens to be a lot of the medicine of today"