Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers.
Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.|Department of Urology, Social Medical Corporation Kojunkai Daido Hospital, Daido Clinic, Nagoya, Japan.
Kazumi
K
Taguchi
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Shuzo
S
Hamamoto
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and a-okada@med.nagoya-cu.ac.jp.
Atsushi
A
Okada
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Rei
R
Unno
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.|Department of Urology, Social Medical Corporation Kojunkai Daido Hospital, Daido Clinic, Nagoya, Japan.
Hideyuki
H
Kamisawa
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Taku
T
Naiki
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Ryosuke
R
Ando
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Kentaro
K
Mizuno
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Noriyasu
N
Kawai
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Keiichi
K
Tozawa
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Kenjiro
K
Kohri
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
Takahiro
T
Yasui
D002129:Calcium Oxalate / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics* / Q000601:surgery; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D002129:Calcium Oxalate
Randall’s plaque; calcium oxalate; ingenuity pathway analysis; kidney stone disease; microarray; renal papilla