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Updated: Jun 8, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue
Jeffrey B Hodgin1, Alain C Borczuk, Samih H Nasr
1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. jhodgin@med.umich.edu
Abstract:
Focal segmental glomerulosclerosis (FSGS) is a common form of idiopathic nephrotic syndrome defined by the characteristic lesions of focal glomerular sclerosis and foot process effacement; however, its etiology and pathogenesis are unknown. We used mRNA isolated from laser-captured glomeruli from archived formalin-fixed, paraffin-embedded renal biopsies, until recently considered an unsuitable source of mRNA for microarray analysis, to investigate the glomerular gene expression profiles of patients with primary classic FSGS, collapsing FSGS (COLL), minimal change disease (MCD), and normal controls (Normal). Amplified mRNA was hybridized to an Affymetrix Human X3P array. Unsupervised (unbiased) hierarchical clustering revealed two distinct clusters delineating FSGS and COLL from Normal and MCD. Class comparison analysis of FSGS + COLL combined versus Normal + MCD revealed 316 significantly differentially regulated genes (134 up-regulated, 182 down-regulated). Among the differentially regulated genes were those known to be part of the slit diaphragm junctional complex and those previously described in the dysregulated podocyte phenotype. Analysis based on Gene Ontology categories revealed overrepresented biological processes of development, differentiation and morphogenesis, cell motility and migration, cytoskeleton organization, and signal transduction. Transcription factors associated with developmental processes were heavily overrepresented, indicating the importance of reactivation of developmental programs in the pathogenesis of FSGS. Our findings reveal novel insights into the molecular pathogenesis of glomerular injury and structural degeneration in FSGS.
Insights
Gene expression profiling reveals key molecular pathways in Focal Segmental Glomerulosclerosis (FSGS). This study identifies differentially regulated genes and developmental programs involved in the pathogenesis of FSGS, offering new insights into kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Focal segmental glomerulosclerosis (FSGS) is a leading cause of idiopathic nephrotic syndrome with unknown etiology and pathogenesis.
- Characteristic lesions include focal glomerular sclerosis and podocyte foot process effacement.
- Traditional methods deemed archived renal biopsies unsuitable for mRNA analysis.
Purpose of the Study:
- To investigate glomerular gene expression profiles in primary FSGS, collapsing FSGS (COLL), minimal change disease (MCD), and normal controls.
- To identify differentially regulated genes and biological pathways implicated in FSGS pathogenesis.
- To explore the utility of laser-captured microdissection and microarray analysis on archival formalin-fixed, paraffin-embedded tissues.
Main Methods:
- Laser-captured microdissection of glomeruli from archival renal biopsies.
- mRNA isolation, amplification, and microarray analysis using an Affymetrix Human X3P array.
- Unsupervised hierarchical clustering and class comparison analyses.
Main Results:
- Hierarchical clustering distinguished FSGS/COLL from Normal/MCD groups.
- 316 significantly differentially regulated genes identified between FSGS+COLL and Normal+MCD groups (134 up, 182 down).
- Overrepresented Gene Ontology categories included development, cell motility, cytoskeleton organization, and signal transduction, with a notable enrichment of developmental transcription factors.
Conclusions:
- Gene expression profiling of laser-captured glomeruli from archival biopsies is feasible and provides valuable insights.
- Reactivation of developmental programs is implicated in the pathogenesis of FSGS.
- Findings reveal novel molecular mechanisms underlying glomerular injury and structural degeneration in FSGS.
