Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria.
BACKGROUND
Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized.


METHODS
Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice.


RESULTS
We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen alpha1, alpha2 (IV) and laminin 10 (laminin alpha 5 beta 1 gamma 1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein interaction network was predicted for podocyte proteins affected by LPS.


CONCLUSIONS
The detected changes in glomerular gene expression and their involvement in protein interaction networks provide putative markers for early and transient glomerular injury and proteinuria.
Sun
Ying
Y
Department of Medical Biochemistry and Biophysics, Division of Matrix Biology, Karolinska Institutet, Stockholm, Sweden.
He
Liqun
L
Takemoto
Minoru
M
Patrakka
Jaakko
J
Pikkarainen
Timo
T
Genové
Guillem
G
Norlin
Jenny
J
Truvé
Katarina
K
Tryggvason
Karl
K
Betsholtz
Christer
C
D000818:Animals; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D050533:Glomerular Basement Membrane / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D050199:Podocytes / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism*
D007797:Laminin; D008070:Lipopolysaccharides; D003094:Collagen