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Immunohistochemical Analysis of Macrophages, Myofibroblasts, and Transforming Growth Factor-β Localization during Rat Renal Interstitial Fibrosis Following Long-Term Unilateral Ureteral ObstructionDepartment of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan, yamate{at}jyui.vet.osakafu-u.ac.jp, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G2W1
Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Veterinary Anatomy, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Laboratory of Toxicologic Pathology, Pharmaceuticals Research Center, Kanebo Ltd., 1-5-90 Tomobuchi-cho, Miyakojima-ku, Osaka 534-8666, Japan
Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G2W1
Renal interstitial fibrosis was induced in rats by chronic unilateral ureteral obstruction (UUO). To identify the mechanisms behind the fibrosis, macrophage influx, myofibroblast involvement, and the localization of transforming growth factor-β (TGF-β, a fibrogenic cytokine) were investigated immunohistochemically in rats euthanatized at 0 (controls), 3, 6, 9, 12, and 15 days after UUO. The number of
Key Words: Fibroblast • fibrogenic cytokine • F344 rat • immunostaining • mononuclear cell • renal fibrosis
Toxicologic Pathology, Vol. 26, No. 6,
793-801 (1998) This article has been cited by other articles:
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-smooth muscle actin-positive myofibroblasts began to increase significantly in the medulla from day 3, and the development of medullary fibrosis was confirmed from day 6 by morphometric analysis. From day 9, papillary fibrosis also developed in association with an increased number of myofibroblasts. These myofibroblasts showed a parallel orientation to the mucosal surface of the pelvis. In the medulla and papilla, from day 6 the number of ED1 (primary antibody)-positive macrophages began to increase significantly. There appeared to be a relationship between macrophage influx and myofibroblast involvement. By contrast, in the cortex there was no marked increase in myofibroblasts nor development of fibrotic tissues, regardless of increased number of macrophages from day 6. Immunohistochemically, no staining for TGF-β was found in infiltrating macrophages or myofibroblasts. However, TGF-β was localized on some cortical proximal renal tubules both of normal control and obstructed kidneys in the early stages on days 3, 6, and 9, suggesting that the possible origin of TGF-β may be renal epithelia. However, the staining intensity for TGF-β on the renal epithelia tended to be weakened in advanced obstructed kidneys on days 12 and 15. The likely contribution of TGF-β to the advanced stages of UUO-induced renal fibrosis remains to be determined. 
