Human TGFBR1 adenoviral particles

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)