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Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli
Karin S. Peterson, … , Michael R. Jackson, Robert J. Winchester
Karin S. Peterson, … , Michael R. Jackson, Robert J. Winchester
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1722-1733. https://doi.org/10.1172/JCI19139.
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Article Autoimmunity

Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli

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Abstract

The molecular pathogenesis of focal/diffuse proliferative lupus glomerulonephritis was studied by cDNA microarray analysis of gene expression in glomeruli from clinical biopsies. Transcriptional phenotyping of glomeruli isolated by laser-capture microscopy revealed considerable kidney-to-kidney heterogeneity in increased transcript expression, resulting in four main gene clusters that identified the presence of B cells, several myelomonocytic lineages, fibroblast and epithelial cell proliferation, matrix alterations, and expression of type I IFN–inducible genes. Glomerulus-to-glomerulus variation within a kidney was less marked. The myeloid lineage transcripts, characteristic of those found in isolated activated macrophages and myeloid dendritic cells, were widely distributed in all biopsy samples. One major subgroup of the samples expressed fibrosis-related genes that correlated with pathological evidence of glomerulosclerosis; however, decreased expression of TGF-β1 argued against its role in lupus renal fibrosis. Expression of type I IFN–inducible transcripts by a second subset of samples was associated with reduced expression of fibrosis-related genes and milder pathological features. This pattern of gene expression resembled that exhibited by activated NK cells. A large gene cluster with decreased expression found in all samples included ion channels and transcription factors, indicating a loss-of-function response to the glomerular injury.

Authors

Karin S. Peterson, Jing-Feng Huang, Jessica Zhu, Vivette D’Agati, Xuejun Liu, Nancy Miller, Mark G. Erlander, Michael R. Jackson, Robert J. Winchester

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Figure 1

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Laser-capture microdissection. (A_C) Isolation of a
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Laser-capture microdissection. (A_C) Isolation of a glomerulus by laser-capture microdissection from a hematoxylin and eosin_stained section of a lupus renal biopsy cut 7 μm in thickness. The arrow in A shows a glomerulus prior to capture. Activation by laser of a heat-sensitive film, placed in direct contact with the tissue section, causes the cells located in the path of the laser to adhere to the film, and they can be lifted out of the tissue section. C indicates the successful film transfer of the captured glomerulus used for RNA extraction. B demonstrates the remaining biopsy after laser capture of the glomerulus. Magnification, ∞20.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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