{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:01:14Z","timestamp":1753891274349,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in adults. Given the limited diagnostic options currently available, we performed RNA sequencing (RNA-seq) of urinary cells to identify potential urinary biomarkers for IMN and to investigate its underlying disease mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted RNA-seq analysis on cells isolated from both first-void and second-void morning urine samples. By integrating these data with single-cell RNA sequencing (scRNA-seq) data from IMN and healthy kidney tissues, we performed comprehensive analyses including: Inflammatory index assessment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) functional annotation, Gene Set Enrichment Analysis (GSEA) enrichment analysis, Protein-Protein Interaction (PPI) network construction. Candidate differentially expressed genes (DEGs) were further validated using urinary cell RNA-seq data. Key genes were ultimately identified through Weighted Gene Co-expression Network Analysis (WGCNA) and subsequently verified by immunohistochemical and Quantitative Real-Time PCR (qRT-PCR) experiments of tissue expression patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings demonstrate that the <jats:italic>CALR<\/jats:italic> gene is significantly associated with IMN pathogenesis and progression. Functionally, <jats:italic>CALR<\/jats:italic> plays crucial roles in both immune response (particularly in antigen presentation) and physiological processes (notably in hemoglobin production).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1574852","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T05:14:40Z","timestamp":1749618880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hemoglobin-associated CALR in proximal tubule cells can be used as a biomarker for idiopathic membranous 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