Identification of ATF3 as a Potential Key Biomarker for Hypertensive Nephropathy via Single-Cell Transcriptome Sequencing

Hypertensive Nephropathy (HTN) is a leading cause of end-stage renal disease (ESRD). Its pathogenesis is complex, involving heterogeneous alterations across multiple cell types. Currently, there is a lack of specific biomarkers capable of early detection of renal injury and reflecting molecular pathological characteristics. We performed an integrated analysis of single-cell RNA sequencing (scRNA-seq) data derived from renal tissue samples of HTN patients and healthy controls. Cell subpopulations were identified via dimensionality reduction and clustering, and key genes were screened using differential expression analysis. Furthermore, we employed functional enrichment analysis, non-negative matrix factorization (NMF), pseudotime trajectory analysis, and transcription factor regulatory network analysis to investigate biological functions and cell-type-specific expression patterns. Validation was conducted using both in vivo and in vitro models. We identified a regulatory network centered on activating transcription factor 3 (ATF3) within renal tubular epithelial cells of HTN tissues. Subsequent validation demonstrated that ATF3 is significantly upregulated in HTN, suggesting it serves as a critical stress response factor mediating renal tissue injury. Mechanistically, our data suggests that ATF3 may participate in the pathological progression of HTN by regulating oxidative stress signaling pathways via FOSB. Based on single-cell sequencing and experimental validation, this study identifies ATF3 as a promising key biomarker for HTN and provides a novel molecular target for its diagnosis and targeted therapy.