The TGFBR1 gene, also known as transforming growth factor beta receptor 1, encodes a serine/threonine kinase receptor that plays a key role in the TGF-β signaling pathway. This pathway is essential for regulating multiple cellular processes, including proliferation, differentiation, apoptosis, and extracellular matrix production. TGFBR1 binds to TGF-β ligands and forms a complex with TGFBR2, which in turn initiates downstream signaling cascades, such as the SMAD-dependent pathway. TGFBR1 dysregulation is associated with a variety of diseases, including cancer, fibrosis, and cardiovascular disease, making it a key target for therapeutic and research applications.
Human TGFBR1 adenoviral particles are genetically engineered viral vectors designed to efficiently deliver the TGFBR1 gene to mammalian cells. These particles are based on replication-defective adenoviruses, which ensure safety while maintaining robust transduction capacity. Adenoviral systems offer many advantages, such as broad tropism, high transduction efficiency in both dividing and non-dividing cells, and the ability to achieve high levels of transgene expression. Human TGFBR1 adenoviral particles typically use a strong promoter to drive constitutive expression of TGFBR1, enabling functional studies in cell lines, primary cells, or in vivo models. They are widely used in research areas such as gene overexpression experiments, studies of TGF-β signaling mechanisms, and potential gene therapy development.
Vascular smooth muscle cell (VSMC) proliferation and migration play a key role in the development of arterial remodeling in various vascular diseases, including atherosclerosis, hypertension, and related diseases. Luteolin is a food-derived flavonoid that has protective effects against cardiovascular diseases. Here, researchers investigated whether transforming growth factor-β receptor 1 (TGFBR1) signaling underlies the inhibitory effects of luteolin on VSMC proliferation and migration. They found that luteolin reduced the proliferation and migration of VSMCs, especially A7r5 and HASMC cells, in a dose-dependent manner. In addition, luteolin inhibited the phosphorylation of TGFBR1, Smad2, and Smad3 in a dose-dependent manner. Notably, adenovirus-mediated overexpression of TGFBR1 enhanced the activation of TGFBR1, Smad2, and Smad3 in VSMCs and partially blocked the inhibitory effects of luteolin on TGFBR1, Smad2, and Smad3. Furthermore, TGFBR1 overexpression rescued the inhibitory effects of luteolin on VSMC proliferation and migration. Molecular dynamics simulations indicated that TGFBR1-luteolin binding was stable. Taken together, these data suggest that luteolin may inhibit VSMC proliferation and migration by inhibiting TGFBR1 signaling.
Here, researchers determined whether the inhibitory effect of luteolin on VSMC migration was attributed to the inhibition of TGFBR1 activation. TGFBR1 was overexpressed in A7r5 and HASMC cells using Ad-TGFBR1, and the anti-migratory effect of luteolin was measured by wound healing and Transwell assays. As shown in Figure 1A-C, overexpression of TGFBR1 significantly enhanced the migration of luteolin-treated A7r5 and HASMC cells. Overexpression of TGFBR1 consistently partially blocked the inhibitory effect of luteolin on the number of migrating cells, and this difference was statistically significant (Figure 1D-F). These findings also suggest that the inhibitory effect of luteolin on VSMC migration is at least partially due to the inhibition of TGFBR1 activation.
Figure 1. Overexpression of TGFBR1 partially blocks the inhibitory effect of luteolin on vascular smooth muscle cell (VSMC) migration. (Wu Y T, et al., 2018)
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Consistent Experimental Results
Used these particles in multiple experiments, and the overexpression of TGFBR1 was consistently successful. The reproducibility is impressive—great for long-term research projects.
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