Diabetic Nephropathy (DN) and Membranous Nephropathy (MN) are two kidney diseases with different etiologies that can manifest to develop into nephrotic syndrome. A pilot study was employed to preliminarily investigate hallmarks, potential biomarkers, and drugs, with the aim of exploring the demarcation and congruity between DN and MN. The analysis was conducted on a small sample cohort (GSE51674) derived from patients with Type 2 Diabetes Mellitus, comprising microRNA (miRNA) expression profiles from 4 normal kidney samples, 6 DN samples, and 6 MN samples. This data was subjected to statistical analysis in R-Studio, enrichment analysis using QIAGEN Ingenuity Pathway Analysis, drug repurposing study using the Schrödinger platform, and in silico validation by the Nephroseq database. The target mRNAs identified in the analysis mapped to typical nephropathy hallmarks, including angiogenesis, immune response, proliferation, apoptosis, and inflammation, as well as to the atypical nephropathy hallmarks, viz., fibrosis, podocyte injury, insulin regulation and response to glucose levels, glomerulosclerosis, and proteinuria. These hallmarks reflect key biological processes implicated in nephropathy progression. Based on their involvement in hallmarks and top pathways, potential miRNAs and mRNA targets were identified. PIK3C2A was identified as a putative therapeutic target, while JUN emerged as a potential prognostic biomarker. This sets a precedent for further in silico and wet-lab investigations to enhance the clinical strategies of DN and MN.
Jain et al. (Sun,) studied this question.