706 RENAL MACROPHAGE MIGRATION AND CRYSTAL PHAGOCYTOSIS VIA INFLAMMATORY-RELATED GENE EXPRESSION DURING KIDNEY STONE FORMATION AND ELIMINATION IN MICE

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112049 RENAL MACROPHAGE MIGRATION AND CRYSTAL PHAGOCYTOSIS VIA INFLAMMATORY-RELATED GENE EXPRESSION DURING KIDNEY STONE FORMATION AND ELIMINATION IN MICE Atsushi Okada, Takahiro Yasui, Jun Ichikawa, Kazunori Nakaoka, Yasuhiko Hirose, Kazumi Taguchi, Kazuhiro Niimi, Yasuhiro Fujii, Masayuki Usami, Takahiro Kobayashi, Ryosuke Ando, Shuzo Hamamoto, Masahito Hirose, Yasunori Itoh, Keiichi Tozawa, and Kenjiro Kohri Atsushi OkadaAtsushi Okada Nagoya, Japan More articles by this author , Takahiro YasuiTakahiro Yasui Nagoya, Japan More articles by this author , Jun IchikawaJun Ichikawa Nagoya, Japan More articles by this author , Kazunori NakaokaKazunori Nakaoka Nagoya, Japan More articles by this author , Yasuhiko HiroseYasuhiko Hirose Nagoya, Japan More articles by this author , Kazumi TaguchiKazumi Taguchi Nagoya, Japan More articles by this author , Kazuhiro NiimiKazuhiro Niimi Nagoya, Japan More articles by this author , Yasuhiro FujiiYasuhiro Fujii Nagoya, Japan More articles by this author , Masayuki UsamiMasayuki Usami Nagoya, Japan More articles by this author , Takahiro KobayashiTakahiro Kobayashi Nagoya, Japan More articles by this author , Ryosuke AndoRyosuke Ando Nagoya, Japan More articles by this author , Shuzo HamamotoShuzo Hamamoto Nagoya, Japan More articles by this author , Masahito HiroseMasahito Hirose Nagoya, Japan More articles by this author , Yasunori ItohYasunori Itoh Nagoya, Japan More articles by this author , Keiichi TozawaKeiichi Tozawa Nagoya, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2280AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We previously established a mouse kidney stone formation model and the generated calcium oxalate crystal deposits could be eliminated after several days, and indicated a susceptibility in which monocyte/macrophage interaction could participate in the phenomenon. To clarify the macrophage-related factors playing roles in the prevention of crystal formation in mouse kidneys, morphological and expression studies based on microarray pathway analysis were performed. METHODS Eight-week-old male C57BL/6 mice were intraabdominally administered 80 mg/kg glyoxylate. The kidneys and urine were obtained every 3 days until day 15. Stone formation was confirmed by Pizzolato staining and the amount of crystallization was calculated. Biotin-labeled cRNAs were synthesized from total RNA extracted from kidney specimens, and then hybridized on Affmetrix Mouse Genome 430 2.0 arrays. The fluorescent intensity of each spot was squantified and analyzed with GeneSpring® software. Based on the raw data of microarray analysis, pathway analyses and quantitative PCR-based association analyses were performed. Immunohistochemical staining of macrophage-related proteins and transmission electron microscopy (TEM) were performed. RESULTS Kidney calcium oxalate crystal depositions increased by day 6, thereafter decreased gradually and had almost disappeared at day 15. In microarray expression data, 18,064 genes demonstrated a significant expression value. Pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokines. Association analysis of related gene expression values indicated the high association of chemokine (C-C) ligand 2, Cd44, colony stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1 and TGF-beta 1 both with the amount of renal crystals and F4/80, a macrophage marker. Immunohistochemically, interstitial macrophages increased and CD44 and MHC-class II were upregulated around crystal formation sites. TEM indicated interstitial macrophage migration with the phagocytosis of crystals. CONCLUSIONS Increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte/macrophage migration and phagocytosis via the interaction of CD44 to osteopontin and fibronectin. Such crystal-removing ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e820 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Atsushi Okada Nagoya, Japan More articles by this author Takahiro Yasui Nagoya, Japan More articles by this author Jun Ichikawa Nagoya, Japan More articles by this author Kazunori Nakaoka Nagoya, Japan More articles by this author Yasuhiko Hirose Nagoya, Japan More articles by this author Kazumi Taguchi Nagoya, Japan More articles by this author Kazuhiro Niimi Nagoya, Japan More articles by this author Yasuhiro Fujii Nagoya, Japan More articles by this author Masayuki Usami Nagoya, Japan More articles by this author Takahiro Kobayashi Nagoya, Japan More articles by this author Ryosuke Ando Nagoya, Japan More articles by this author Shuzo Hamamoto Nagoya, Japan More articles by this author Masahito Hirose Nagoya, Japan More articles by this author Yasunori Itoh Nagoya, Japan More articles by this author Keiichi Tozawa Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...