Title : TGF-B signaling in smooth muscle differentiation and vascular remodeling
Vascular smooth muscle (SM) plays a fundamental role in embryonic development and in adult life, whereas abnormal SM differentiation or phenotypic modulation is associated with congenital heart diseases, atherosclerosis, restenosis following angioplasty, post-transplant vasculopathy, and hypertension. SM differentiation is the differentiation of mature SM from progenitors, while SM phenotype modulation is a process that the mature SM loses their contractile phenotype and acquires a synthetic/proliferative phenotype due to the down-regulation of SM contractile proteins. During the vasculogenesis or angiogenesis, SM progenitors are recruited to the endothelial cell (EC) tube, where they differentiate to SM under the stimulation of various growth factors/cytokines. The newly differentiated SMC participates in the regulation of vasculogenesis or angiogenesis by limiting the excessive EC tube formation. SM could also produce different factors regulating the function of newly formed blood vessel. TGF-β plays a critical role in SM differentiation because knockout of TGF-β ligand, receptors, co-receptors, or downstream signaling molecules causes vascular defects during embryonic development due to the impaired SM differentiation. TGF-β activates both Smad2 and Smad3. Knockout of Smad3 has no major impact on vascular development. However, knockout of Smad2 causes early embryonic lethality. By using neural crest and SM tissue-specific knockout strategy, we found that Smad2 plays an essential role in SM differentiation from neural crest cells. I will discuss the mechanism underlying TGF-β signaling in regulating SMC differentiation from neural crest cells and mesenchymal progenitors and the use of tissue-specific knockout approach to delineate the development of SM during embryonic development and SM function in adult vessels.
Audience take away:
- The roles of smooth muscle in vasculogenesis and angiogenesis.
- Diversity of smooth muscle progenitors.
- Signaling pathways that mediate TGF-β function.
- The role of Smad2 in smooth muscle differentiation.
- Smad2 regulation of smooth muscle function in adult blood vessel.