| First Author | Wang M | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 23 | PubMed ID | 38069081 |
| Mgi Jnum | J:343693 | Mgi Id | MGI:7566598 |
| Doi | 10.3390/ijms242316756 | Citation | Wang M, et al. (2023) TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury. Int J Mol Sci 24(23) |
| abstractText | Acute lung injury (ALI) is characterized by endothelial barrier disruption and associated inflammatory responses, and transient receptor potential cation channel 6 (TRPC6)-mediated Ca(2+) influx is critical for endothelial hyperpermeability. In this study, we investigated the role of TRPC6 in LPS-induced ALI, analyzed gene expression in WT and TRPC6(-/-) lungs using RNA sequencing, and explored the effects of TRPC6 in the LPS-induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) to elucidate the underlying mechanisms. Intratracheal instillation of LPS caused edema in the mouse lungs. Deletion of TRPC6 reduced LPS-induced lung edema and decreased cell infiltration. RNA sequencing analysis suggested that downregulated cell adhesion molecules in TRPC6(-/-) lungs may be responsible for their resistance to LPS-induced injury. In addition, downregulation of TRPC6 significantly alleviated the LPS-induced decrease in eNOS expression in lung tissue as well as in HUVECs. Moreover, inhibition of TRPC6 with the channel antagonist larixyl led to a decrease in LPS-induced hyperpermeability and ROS production in HUVECs, which could be reversed by blocking eNOS. Our findings suggest that inhibition of TRPC6 ameliorates LPS-induced ALI, which may be achieved by acting on the cell adhesion molecule signaling pathway and participating in the regulation of eNOS levels in endothelial cells. |
