A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue

Jeffrey B. Hodgin, Alain C. Borczuk, Samih H. Nasr, Glen S. Markowitz, Viji Nair, Sebastian Martini, Felix Eichinger, Courtenay Vining, Celine C. Berthier, Matthias Kretzler, Vivette D. D'Agati

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1674-1686
Number of pages13
JournalAmerican Journal of Pathology
Volume177
Issue number4
DOIs
StatePublished - Oct 2010
Externally publishedYes

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Focal Segmental Glomerulosclerosis
Paraffin
Formaldehyde
Lipoid Nephrosis
Messenger RNA
Cell Movement
Biological Phenomena
Podocytes
Gene Ontology
Sclerosis
Microarray Analysis
Diaphragm
Cytoskeleton
Morphogenesis
Transcriptome
Genes
Cluster Analysis
Foot
Signal Transduction
Lasers

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Hodgin, J. B., Borczuk, A. C., Nasr, S. H., Markowitz, G. S., Nair, V., Martini, S., ... D'Agati, V. D. (2010). A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue. American Journal of Pathology, 177(4), 1674-1686. https://doi.org/10.2353/ajpath.2010.090746

A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue. / Hodgin, Jeffrey B.; Borczuk, Alain C.; Nasr, Samih H.; Markowitz, Glen S.; Nair, Viji; Martini, Sebastian; Eichinger, Felix; Vining, Courtenay; Berthier, Celine C.; Kretzler, Matthias; D'Agati, Vivette D.

In: American Journal of Pathology, Vol. 177, No. 4, 10.2010, p. 1674-1686.

Research output: Contribution to journalArticle

Hodgin, JB, Borczuk, AC, Nasr, SH, Markowitz, GS, Nair, V, Martini, S, Eichinger, F, Vining, C, Berthier, CC, Kretzler, M & D'Agati, VD 2010, 'A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue', American Journal of Pathology, vol. 177, no. 4, pp. 1674-1686. https://doi.org/10.2353/ajpath.2010.090746
Hodgin, Jeffrey B. ; Borczuk, Alain C. ; Nasr, Samih H. ; Markowitz, Glen S. ; Nair, Viji ; Martini, Sebastian ; Eichinger, Felix ; Vining, Courtenay ; Berthier, Celine C. ; Kretzler, Matthias ; D'Agati, Vivette D. / A molecular profile of focal segmental glomerulosclerosis from formalin-fixed, paraffin-embedded tissue. In: American Journal of Pathology. 2010 ; Vol. 177, No. 4. pp. 1674-1686.
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