Abstract
BackgroundHypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease, yet the precise mechanisms and cell-specific gene expression changes are still unknown. This study used single-cell RNA sequencing (scRNA-seq) to explore novel molecular mechanisms and gene targets for HTN for the first time. Methods: The gene expression profiles of renal biopsy samples obtained from HTN patients and healthy living donor controls were determined by scRNA-seq technology. Distinct cell clusters, differential gene expression, cell-cell interaction and potential signaling pathways involved in HTN were determined. Results18 distinct cell clusters were identified in kidney from HTN and control subjects. Endothelial cells overexpressed LRG1 , a pleiotropic factor linked to apoptosis and inflammation, providing a potential novel molecular target. HTN endothelium also overexpressed genes linked to cellular adhesion, extracellular matrix accumulation and inflammation. In HTN patients, mesangial cells highly expressed proliferation related signatures ( MGST1 , TMSB10, EPS8 and IER2 ) not detected in renal diseases before. The upregulated genes in tubules of HTN were mainly participating in inflammatory signatures including IFN-γ signature, IL-17 signaling and TLR signaling. Specific gene expression of kidney-resident CD8 + T cells exhibited a proinflammatory, chemotactic and cytotoxic phenotype. Furthermore, receptor-ligand interaction analysis indicated cell-cell crosstalk in kidney contributes to recruitment and infiltration of inflammatory cells into kidneys, and fibrotic process in hypertensive renal injury. ConclusionsIn summary, our data identifies a distinct cell-specific gene expression profile, pathogenic signaling pathways and potential cell-cell communications in the pathogenesis of HTN. These findings will provide a promising novel landscape for mechanisms and treatment of HTN.
Cell–cell crosstalk in the heart
