Fluid shear stress inhibits vascular endothelial cells proliferation via EGR1/Grem1 axis

Pulmonary hypertension (PH) is associated with fluid shear stress (FSS) and Gremlin1 (Grem1), but the mechanism by which FSS acts on Grem1 remains unclear. Here we found that FSS downregulated Grem1 in bEnd.3 cells. Meanwhile, FSS inhibited the expression of transcription factor EGR1. Mechanistically, FSS inhibited the transcriptional activity of Grem1 promoter by down-regulating EGR1. RNA-seq and cell function analysis indicated that FSS inhibited the cell cycle and proliferation through the EGR1/Grem1 axis in bEnd.3 cells. In addition, FSS also down-regulated the expression of Grem1 and EGR1 in mouse/rat pulmonary microvascular endothelial cells. Together, our findings revealed the mechanism by which FSS inhibited the cell cycle and proliferation of vascular endothelial cells through the EGR1/Grem1 axis, providing new insights into the development of PH.