biostudies-literatureUnknown27(1)Bhayana SIdiopathic nephrotic syndrome (NS) is a common glomerular disease. Although glucocorticoids (GC) are the primary treatment, the PPARγ agonist pioglitazone (Pio) also reduces proteinuria in patients with NS and directly protects podocytes from injury. Because both drugs reduce proteinuria, we hypothesized these effects result from overlapping transcriptional patterns. Systems biology approaches compared glomerular transcriptomes from rats with PAN-induced NS treated with GC vs. Pio and identified 29 commonly regulated genes-of-interest, primarily involved in extracellular matrix (ECM) remodeling. Correlation with clinical idiopathic NS patient datasets confirmed glomerular ECM dysregulation as a potential mechanism of injury. Cellular deconvolution <i>in silico</i> revealed GC- and Pio-induiScience108631https://www.ebi.ac.uk/biostudies/studies/S-EPMC10770536biostudies-literatureGlucocorticoid- and pioglitazone-induced proteinuria reduction in experimental NS both correlate with glomerular ECM modulation.PMC10770536Agrawal SFitch JWijeratne SWolfgang KJBhayana SKerlin BAWaller APSmoyer WEWhite PDougherty JAKamigaki YfalseGlucocorticoid- and pioglitazone-induced proteinuria reduction in experimental NS both correlate with glomerular ECM modulation.Idiopathic nephrotic syndrome (NS) is a common glomerular disease. Although glucocorticoids (GC) are the primary treatment, the PPARγ agonist pioglitazone (Pio) also reduces proteinuria in patients with NS and directly protects podocytes from injury. Because both drugs reduce proteinuria, we hypothesized these effects result from overlapping transcriptional patterns. Systems biology approaches compared glomerular transcriptomes from rats with PAN-induced NS treated with GC vs. Pio and identified 29 commonly regulated genes-of-interest, primarily involved in extracellular matrix (ECM) remodeling. Correlation with clinical idiopathic NS patient datasets confirmed glomerular ECM dysregulation as a potential mechanism of injury. Cellular deconvolution <i>in silico</i> revealed GC- and Pio-indu2024-01-01T00:00:00Z2024 Jan2025-04-18T18:47:32.561Z2025-04-07T06:29:47.656ZS-EPMC107705363818851210.1016/j.isci.2023.108631