The Neuronal Transcription Factor Creb3l1 Potential Upregulates Ntrk2 in the Hypertensive Microenvironment to Promote Vascular Smooth Muscle Cell-Neuron Interaction and Prevent Neurons from Ferroptosis: A Bioinformatic Research of scRNA-seq Data.

Abstract

Background There is still a lack of knowledge regarding the association between hypertension and ferroptosis. A single-cell approach was used to study the changes in neuropeptide expression as they might contribute to the mechanisms leading to ferroptosis in a hypertensive microenvironment. Methods We analyzed 11798 cells from the SHR group and 12589 cells from the WKY group of mouse arterial cells. CellPhoneDB was used for cell communication analysis, and the SCENIC method was used to identify key transcription factors in neurons. The correlation between Ntrk2 and ferroptosis-related genes was further analyzed and validated via quantitative polymerase chain reaction. Results The arterial cells were clustered into six cell types. Ligand-receptor analysis suggested that Ngf, Ntf3, Cxcr4, and Ntrk2 were key neuropeptide-related genes involved in the communication between vascular smooth muscle cells and neural cells. In the hypertensive microenvironment, the neuronal transcription factor Creb3l1 appears to play a key role in the upregulation of Ntrk2 to promote the interaction between neurons and vascular smooth muscle cells. An association between Ntrk2 and the ferroptosis death inhibitor Gpx4 was suggested. RT-qPCR experiments confirmed that Ntrk2 downregulation in neural cells was followed by downregulated expression of Gpx4. Conclusions Creb3l1, a key transcription factor in vascular neurons, may upregulate Ntrk2 to promote vascular smooth muscle cell-neuron interaction and thereby potentially prevent ferroptosis in neurons.