title: A prostacyclin analog prevents the regression of renal microvascular network by inhibiting mitochondria-dependent apoptosis in the kidney of rat progressive glomerulonephritis.
abstract: We have previously demonstrated that renoprotective effects of a prostacyclin analog, beraprost sodium, on the kidney of anti-glomerular basement membrane glomerulonephritis (GN) rats. The aim of this study is to address the renoprotection mechanism of beraprost sodium, especially in the terminal stage of GN. Beraprost sodium was orally administrated from 2 to 7 weeks after induction of GN, and renal function, morphology, protein and mRNA levels were analyzed. We found the beraprost sodium treatment suppressed the structural regression of renal microvascular network and decline of renal blood flow occurred in the kidney of GN rats. To address the mechanism of the structural maintenance, we focused on apoptosis because the increased number of apoptotic renal microvascular endothelial cells and tubular epithelial cells was observed in the kidneys of GN rats as compared with normal and beraprost sodium treated rats. Protein and mRNA analyses demonstrated that mitochondria-dependent apoptotic pathway was activated in the kidneys of GN rats, and beraprost sodium suppressed the activation by modulating the expression patterns of pro- and anti-apoptotic factors. These results suggest that inhibition of mitochondria-dependent apoptosis of renal cells in GN kidney and consequent maintenance of renal functional structures, including microvascular network might contribute to the renoprotective effect of beraprost sodium in GN.
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan. Electronic address: Yasufumi_Goto@nts.toray.co.jp.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Hajimu
authors.initials: H
authors.lastname: Kurumatani
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okano
authors.affiliation: Toray Industries, Inc., Pharmaceutical Research Laboratories, Kamakura, Kanagawa, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002196:Capillaries; D020169:Caspases / Q000032:analysis; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D050533:Glomerular Basement Membrane / Q000276:immunology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007106:Immune Sera / Q000008:administration & dosage; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology; D008928:Mitochondria / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D007106:Immune Sera; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C494837:Xiap protein, rat; D051028:bcl-2-Associated X Protein; C048081:beraprost; D011464:Epoprostenol; D020169:Caspases
keywords: Apoptosis; Beraprost sodium; Chronic kidney diseases; Microvascular network; Prostacyclin analog; Rat anti-glomerular basement membrane glomerulonephritis