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| 1.
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論文
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Sakai, Norihiko ; Furuichi, Kengo ; Shinozaki, Yasuyuki ; Yamauchi, Hiroyuki ; Toyama, Tadashi ; Kitajima, Shinji ; Okumura, Toshiya ; Kokubo, Satoshi ; Kobayashi, Motoo ; Takasawa, Kazuya ; Takeda, Shin-ichi ; Yoshimura, Mitsuhiro ; Kaneko, Shuichi ; Wada, Takashi
概要:
金沢大学医薬保健研究域医学系<br />The presence of chronic kidney disease in humans is associated with a risk of kidney function loss a
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s well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2. © 2010 Elsevier Inc. All rights reserved.
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| 2.
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Wada, Takashi ; Sakai, Norihiko ; Sakai, Yoshio ; Matsushima, Kouji ; Kaneko, Shuichi ; Furuichi, Kengo
概要:
金沢大学医薬保健研究域医学系<br />Cellular mechanisms have been proposed in the pathogenesis of fibrotic processes in the kidney. In t
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his setting, cell sources underlying the generation of matrix-producing cells in diseased kidneys have been categorized as activated resident stromal cells (e.g., fibroblasts, pericytes), infiltrating bone-marrow-derived cells (e.g., fibrocytes, T cells, macrophages), and cells derived from epithelial-mesenchymal transition/endothelial-mesenchymal transition. Among these cell sources, accumulating evidence has shed light on the involvement of bone-marrow-derived cells, including monocytes/macrophages, and a circulating mesenchymal progenitor cell, fibrocyte, in the progression of fibrosis in kidney. Bone-marrow-derived cells positive for CD45 or CD34, and type 1 (pro)collagen dependent on the chemokine and renin-angiotensin systems migrate into diseased kidneys and enhance synthesis matrix protein, cytokines/chemokines, and profibrotic growth factors, which may promote and escalate chronic inflammatory processes and possible interaction with resident stromal cells, thereby perpetuating kidney fibrosis. © 2010 Japanese Society of Nephrology.
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Wada, Takashi ; Yokoyama, Hitoshi ; Sakai, Norihiko ; Izumiya, Yoshiaki ; Shimizu, Miho ; Furuichi, Kengo ; Segawa, Chikako ; Misaki, Tsuguho ; Kobayashi, Ken-ichi
概要:
We describe the upregulation of cytokines in a 45-year-old woman with tubulointerstitial nephritis and membranous nephro
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pathy revealed by renal biopsy. She was treated with a combination of prednisolone and cyclosporin. Histological findings showed appreciable improvement, and urinary protein excretion was decreased from 15 g/day to 1 g/day. Elevated urinary levels of chemokines, interleukin (IL)-8 and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1, and serum levels of tumor necrosis factor (TNF)-α decreased during convalescence; 13 other patients with membranous nephropathy did not show elevation of these cytokines. These results suggest that the upregulation of these cytokines may participate in the pathogenesis of tubulointerstitial nephritis and that combination therapy of prednisolone and cyclosporin may be effective, possibly via inducing a decrease in these cytokines.
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| 4.
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論文
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Wada, Takashi ; Sakai, Norihiko ; Matsushima, Kouji ; Kaneko, Shuichi
概要:
金沢大学医学部附属病院血液浄化療法部<br />Fibrocytes are supposed to be a circulating connective tissue cell progenitor, which consists of
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a novel population of peripheral blood cells. This distinct population of blood-borne cells shares markers of leukocytes as well as mesenchymal cells. Accumulating evidence indicates that fibrosis is characteristic of progressive chronic kidney diseases of any etiologies, resulting in kidney failure. We have uncovered that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to kidney fibrosis induced by unilateral ureteral obstruction in mice. In addition, the blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced kidney fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in macrophage recruitment along with reduced renal transcripts of monocyte chemoattractant protein-1 (MCP-1/CCL2). These findings suggest that fibrocytes dependent on CCL21/CCR7 signaling pathways contribute to the pathogenesis of kidney fibrosis, thereby providing that regulating fibrocytes may provide a novel therapeutic benefit for kidney fibrosis. © 2007 International Society of Nephrology.
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Wada, Takashi ; Yokoyama, Hitoshi ; Matsushima, Koji ; Kobayashi, Kenichi ; 和田, 隆志
概要:
The interaction of activated leukocytes and renal resident cells is thought to play a crucial role in the pathogenesis of renal diseases. Recent investigations of the pathophysiological roles of chemokines and their cognate receptors have
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shed light on the detailed molecular mechanisms of leukocyte trafficking and activation in the diseased kidneys. Chemokine/chemokine receptor systems may be essentially involved in the pathogenesis of phase-specific renal disorders and the measurement of urinary levels of chemokines may be clinically useful for monitoring the different disease phases and activities. In addition, chemokine receptors expressed in renal resident cells may be involved in proliferation, fibrogenesis, as well as chemotaxis. The selective intervention of chemokine/chemokine receptor systems (anti-chemokine therapy) may have the potential as the particular therapeutic strategies for renal diseases in future
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