KLF2 promoter luciferase assays in COS-7 cells were performed as we described in methods section. Among the positive hit compounds, we observed that TA significantly increased KLF2 promoter luciferase activity at 5 µM (data not shown). The structure of TA is shown in Fig. 1A. Dose dependent assay showed that TA significantly increased KLF2 promoter luciferase activity at 10 and 20 µM (Fig. 1B). Simvastatin (1 µM), which was previously reported as a KLF2 activator21, 24, was used as a positive control. Next, the effect of TA on KLF2 was then confirmed by qPCR assay. KLF2 downstream target gene ET-1 was also examined. As shown in Fig. 2A, TA could increase KLF2 mRNA expression in HCAECs in a concentration-dependent manner. Meanwhile, TA significantly decreased ET-1 mRNA expression at 10 and 20 μM (Fig. 2B). Overall, our data suggest that TA is a KLF2 activator.Figure 1Identification of TA as a KLF2 activator. (A) Chemical structure of the TA. (B) KLF2 luciferase activity was analyzed in COS-7 cells transfected with KLF2-luciferase plasmids treatment with DMSO (vehicle), TA (0.1, 1.0, 10 and 20 μM) or simvastatin (1.0 μM). **P < 0.01, Student’s t test. Values represent mean ± SEM; n = 4. Figure 2TA induced KLF2 expression in HCAECs. (A,B) HCAEC cells were treated with DMSO, TA (0.1, 1, 10 and 20 μM), or simvastatin (1.0 μM) for 24 h, then KLF2 (A) and ET-1 (B) mRNA expression was detected by qPCR. **P < 0.01, *P < 0.05 (TA or vs vehicle), Student’s t test. Values represent mean ± SEM; n = 4.