Panoply™ Human EGR1 Knockdown Stable Cell Line

Mesenchymal stem cells (MSCs) can differentiate into endothelial cells, yet the mechanisms underlying this process within the tumor microenvironment (TME) remain unclear. Here, researchers demonstrate that tumor necrosis factor-alpha (TNF-α)-a key cytokine in the TME-promotes the differentiation of MSCs into endothelial cells by inducing the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) gene. EGR1 is a member of the zinc-finger transcription factor family induced by TNF-α. The results show that EGR1 directly binds to the VEGFR2 promoter region and transactivates VEGFR2 expression. Furthermore, the researchers confirmed that upon TNF-α stimulation, EGR1 forms a complex with c-JUN (activated by c-JUN N-terminal kinase, or JNK), thereby promoting VEGFR2 transcription and endothelial differentiation in MSCs. Silencing EGR1 or c-JUN using shRNA blocks TNF-α-induced VEGFR2 transcription and the endothelial differentiation of MSCs.

To further confirm the role of EGR1 in regulating VEGFR2 expression, researchers generated a stable EGR1-knockdown BM-MSC cell line. Compared with control cells, the TNF-α-induced expression of VEGFR2 and VCAM-1 (an endothelial marker) was significantly inhibited in EGR1-knockdown cells (Figure 1A). Furthermore, EGR1 silencing reduced the formation of TNF-α-induced endothelial-like tubular structures (Figure 1B) and the length of these structures (Figure 1C). Thus, EGR1 plays a crucial role in TNF-α-induced endothelial differentiation of BM-MSCs by regulating VEGFR2 expression.

Figure 1. EGR1 regulates TNF-α-induced VEGFR2 expression and the endothelial differentiation of BM-MSCs. (Jung E, et al., 2023)