Transforming growth factor-β dynamically regulates vascular smooth muscle differentiation in vivo

• DOI: 10.1242/jcs.111.19.2977
• Publication Date: 2021-04-24T03:01:36Z
• Authors: David J. Grainger; James C. Metcalfe; Andrew A. Grace; David E. Mosedale
• Keywords: 0301 basic medicine; Heterozygote; Cell Differentiation; Muscle Development; Mice, Mutant Strains; Muscle, Smooth, Vascular; Rats; Mice, Inbred C57BL; Mice; Tamoxifen; 03 medical and health sciences; Carotid Arteries; Transforming Growth Factor beta; Animals; Female; Rats, Wistar; Carotid Artery Injuries; Gene Deletion

ABSTRACT Variations in the levels of smooth muscle-specific isoforms of contractile proteins have been reported to occur in many different vascular diseases. However, although much work has been done in vitro to investigate the regulation of smooth muscle cell differentiation, the molecular mechanisms which regulate the differentiation of vascular smooth muscle tissue in vivo are unknown. Using quantitative immunofluorescence, we show that in rat arteries levels of smooth muscle differentiation markers correlate with the levels of the cytokine TGF-β. In young mice with one allele of the TGF-β1 gene deleted, the levels of both TGF-β1 and smooth muscle differentiation markers are reduced compared to wild-type controls. This regulation of smooth muscle differentiation by TGF-β?during post-natal development also occurs dynamically in the adult animal. Following various pharmacological or surgical interventions, including treatment of mice with tamoxifen and balloon injury of rat carotid arteries, there is a strong correlation between the changes in the levels of TGF-β and changes in the levels of smooth muscle differentiation markers (r=0.9, P<0.0001 for n=26 experiments). We conclude that TGF-β dynamically regulates smooth muscle differentiation in rodent arteries in vivo.