骨调素反义RNA在培养的肾小管上皮细胞的表达

骨调素（ｏｓｔｅｏｐｏｎｔｉｎ,ＯＰＮ）是含精氨酸·甘氨酸－天门冬氨酸（ＲＧＤ）三肽序列（黏附分子结构）的高度酸性的磷酸化分泌性糖蛋白,是很强的巨噬细胞化学趋化和黏附分子。在许多与肾小管间质炎症损伤和纤维化有关的实验动物模型中,肾小管上皮细胞均有ＯＰＮ的过度表达,巨噬细胞浸润均发生在肾小管上皮细胞过度表达ＯＰＮ的区域,肾小管上皮细胞ＯＰＮ的过度表达与巨噬细胞局部浸润的密切相关性,表明ＯＰＮ是介导巨噬细胞在肾小管浸润并导致炎症损伤和纤维化发生和发展的关键细胞因子。因此,如能阻断肾小管上皮细胞ＯＰＮ…     

骨调素对巨噬细胞在新月体肾炎肾脏组织局部浸润的影响

目的观察骨调素（ＯＰＮ）在大鼠实验性新月体肾炎肾脏组织中的表达及功能性抑制ＯＰＮ的活性对巨噬细胞在肾脏局部浸润的影响。方法ＯＰＮ在肾脏组织蛋白和基因水平的表达分别应用免疫组化双标记及原位杂交技术。结果在实验性新月体肾炎肾脏组织内ＯＰＮ的表达明显升高，并与肾脏局部巨噬细胞的浸润、肾脏病理损害程度及肾功能的下降明显相关。应用抗ＯＰＮ抗体治疗以后可显著抑制ＯＰＮ在肾脏组织的表达，同时巨噬细胞在肾脏组织局部的浸润也明显减少，肾脏病理损害减轻、肾功能明显改善。结论ＯＰＮ的高表达是实验性新月体肾炎发病过程中巨噬细胞在肾脏组织局部浸润的重要介导因子，抑制ＯＰＮ的表达和功能可显著抑制肾脏局部巨噬细胞的聚集及改善肾功能。     

CD44及其配体骨调素在大鼠实验性新月体肾炎中的表达及作用

目的探讨ＣＤ４４及其配体骨调素（ＯＰＮ）在实验性新月体肾炎发展过程中的表达和作用。方法应用兔抗鼠肾毒性血清制作新月体肾炎模型，免疫组化双标记及原位杂交技术检测ＣＤ４４、ＯＰＮ及其它指标。结果ＣＤ４４和ＯＰＮ在新月体肾炎的发展过程中表达明显升高，并和巨噬细胞在肾脏组织的局部浸润、新月体的形成及肾功能的损害密切相关。结论在实验性新月体肾炎模型，ＣＤ４４和ＯＰＮ在肾小球实质细胞和小管间质细胞显著表达，并可能在新月体肾炎的发病过程中发挥重要的作用。     

PCNA反义寡核苷酸抑制膀胱癌细胞BIU-87体外增殖的研究

目的检测脂质体介导增殖细胞核抗原（ＰＣＮＡ）反义寡核苷酸抑制人膀胱癌细胞ＢＩＵ８７体外增殖活性效果。方法采用细胞计数及ＭＴＴ比色法评价反义寡核苷酸对ＢＩＵ８７细胞体外增殖的影响;应用免疫组化法（ＳＡＢＣ法）检测ＰＣＮＡ蛋白表达情况。结果脂质体介导ＰＣＮＡ反义寡核苷酸组与对照组比较,ＢＩＵ８７细胞增殖活性受到明显抑制（Ｐ＜０．０５）,１２小时后可完全抑制ＰＣＮＡ蛋白表达,２４、３６小时后仍有极显著的抑制作用（Ｐ＜０．０１）;脂质体介导反义寡核苷酸组与单纯反义寡核苷酸组比较,前者抑制作用提高５０倍以上;脂质体介导正义寡核苷酸组、单纯脂质体组与对照组比较均无此抑制作用（Ｐ＞０．０５）。结论脂质体介导ＰＣＮＡ反义寡核苷酸可抑制人膀胱癌细胞ＢＩＵ８７体外增殖活性。应用反义技术封闭ＰＣＮＡ基因、抑制ＰＣＮＡ蛋白表达,为膀胱癌的基因治疗提供了新的思路和探索。     

一氧化氮合成酶与高胆固醇血症大鼠肾损害的关系

一氧化氮（ＮＯ）在肾脏生理及病理中起着不可忽视的作用，在糖尿病早期ＮＯ的增多与高滤过高灌注有着密切的联系，且与诱生型一氧化氮合成酶（ｉＮＯＳ）的表达上调相关［１］。在肾炎模型中浸润的巨噬细胞可表达ｉＮＯＳ，它与ＮＯ的增多及肾组织损伤有关［２］。在高胆固醇血症动物模型肾组织中也有浸润的巨噬细胞，肾小管细胞也表达ｉＮＯＳ，那么其中ｉＮＯＳ如何变化，它的变化与脂质肾损害有什么关系，均未见报道。本研究中，我们系统检测了高胆固醇血症大鼠尿、肾皮质ＮＯ变化及肾小管ｉＮＯＳ的表达情况，探讨ｉＮＯＳ与脂质肾损害…     

细胞增殖与凋亡在单侧输尿管梗阻大鼠肾间质纤维化发病中的意义

目的 了解细胞增殖与凋亡在肾小管间质纤维化中的意义。方法 动态观察单侧输尿管梗阻（ＵＵＯ）大鼠模型中梗阻侧肾脏及假手术组肾脏肾小管细胞及间质细胞的增殖细胞核抗原（ＰＣＮＡ）表达及细胞凋亡情况,以及间质α平滑肌肌动蛋白（α－ＳＭＡ）表达水平。结果 ＵＵＯ大鼠梗阻肾从第３天至第１１天,均可见较大量的细胞凋亡,以肾小管上皮细胞居多,其中亦有间质细胞。无论肾小管或间质细胞,ＰＣＮＡ的表达在第３天已达高峰,     

核因子κB反义寡核苷酸对转化生长因子β1诱导人肾小管上皮细胞转分化的影响

目的 探讨在转化生长因子β1（TGF-β1）诱导下，核因子κB（NF-κB）反义寡核苷酸对体外培养的人肾小管上皮细胞（HK-2）转分化的影响。 方法 采用脂质体介导的方法将NF-κB反义寡核苷酸（AS-ODN）导入细胞，以TGF-β1（10 μg/L）刺激HK-2细胞24 h后，用RT-PCR方法检测细胞中NF-κB mRNA及α平滑肌肌动蛋白（α-SMA）mRNA表达，用荧光光谱法分析α-SMA蛋白的表达，并以倒置相差显微镜观察细胞转分化过程的形态变化。 结果 TGF-β1诱导24 h后，HK-2细胞中NF-κB mRNA的表达显著上调，为空白对照组的8倍以上（P < 0.01）。NF-κB反义寡核苷酸导入细胞后，可显著抑制TGF-β1诱导的HK-2细胞的 NF-κB mRNA表达，比TGF-β1组减少75％（P < 0.05），同时，α-SMA mRNA和蛋白表达亦较TGF-β1组均明显下调（P < 0.05）。 结论 NF-κB反义寡核苷酸可抑制TGF-β1诱导肾小管上皮细胞NF-κB的表达，抑制肾小管上皮细胞转分化，可能有利于肾间质纤维化的防治。     

免疫性间质性肾炎动物模型肾组织炎症细胞浸润与细胞间粘附分…

目的 探讨自身免疫性间质性肾炎的发病机理。 方法 用正常小牛肾小管基底膜（ｂＴＢＭ）制造抗ＴＢＭ型ＢＮ大鼠间质肾炎模型，并用单克隆抗体免疫组化ＡＢＣ法、间接免疫荧光技术，检测炎症细胞及细胞间粘附分子－１（ＩＣＡＭ－１）等。 结果 用ｂＴＢＭ免疫后第９天￣３周，均可见肾间质有炎症细胞浸润及肾小管上皮细胞有ＩＣＡＭ－１强烈表达，与病理损害程度有同步现象。 结论 在免疫性间质性肾炎发生发展中，由ＩＣＡＭ     

巨噬细胞与肾损伤

巨噬细胞在炎症的控制中占有主导作用。在细胞因子网络中，单核巨噬细胞能分化并表达不同功能，最终引起组织损伤或修复，各种肾小球肾炎（以下简称肾炎）或肾小管间质炎症均伴有巨噬细胞的明显浸润，研究巨噬细胞在肾损伤中的作用及相关调节因子显得尤其重要，阐明其相互关系有望能探索有效治疗途径。     

急性间质性肾炎的临床和病理研究

急性间质性肾炎的临床和病理研究陈惠萍，黎磊石，王建平ＡＣＬＩＮＩＣＯＰＡＴＨＯＬＯＧＩＣＡＬＳＴＵＤＹＯＮＡＣＵＴＥＩＮＴＥＲＳＴＩＴＩＡＬＮＥＰＨＲＩＴＩＳ（ＡＩＮ）ＣｈｅｎＨｕｉｐｉｎｇ；ＺｈａｎｇＪｉｎｇｈｏｎｇ；ＬｉＬｅｉｓｈｉ，ｅｔａｌ．（...     

Osteopontin expression in acute renal allograft rejection

BACKGROUND: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown. METHODS: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated. RESULTS: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells. CONCLUSION: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.     

Effects of cyclosporine in osteopontin null mice

BACKGROUND: Osteopontin (OPN) is a macrophage adhesive and cell survival factor that is up-regulated in tubules in tubulointerstitial disease. We have previously reported that rats with cyclosporine (CsA) nephropathy have increased tubular osteopontin that correlates with the infiltration of macrophages and interstitial fibrosis. This study tested the hypothesis that the absence of OPN would ameliorate CsA nephropathy. METHODS: OPN knockout (-/-) and wild type (+/+) mice were fed a low salt diet (Na+ 0.01%) for one week and then received daily CsA injections (30 mg/kg, SC) until sacrifice at two weeks. Afferent arteriolopathy, tubulointerstitial injury, macrophage infiltration, collagen III deposition, transforming growth factor-beta (TGF-beta) expression, and tubular and interstitial cell proliferation and apoptosis were evaluated. RESULTS: Wild type mice developed early features of CsA nephropathy, with arteriolar hyalinosis and cortical and tubulointerstitial fibrosis. Despite comparable CsA levels, OPN-/- mice had less arteriolopathy (15 vs. 24%, P < 0.05), a 20% reduction in cortical macrophage infiltration (P < 0.05), and 20% reduction in interstitial collagen deposition (P < 0.05). OPN-/- mice also showed less cortical interstitial cell proliferation but no differences in tubular cell proliferation or apoptosis. OPN+/+ mice also developed some neurotoxicity, consisting of ataxia, and this was associated with increased mortality at two weeks. CONCLUSION: OPN partially mediates arteriolopathy, early macrophage recruitment and fibrosis in murine CsA nephropathy. OPN also may be involved in CsA associated neurotoxicity.     

Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process

BACKGROUND: There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. METHODS: A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. RESULTS: In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P < 0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. CONCLUSIONS: These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.     

Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis.

BACKGROUND: Osteopontin is a macrophage adhesive protein that is expressed by renal tubules in tubulointerstitial disease. METHODS: To investigate the function of OPN, we induced tubulointerstitial disease in OPN null mutant (OPN-/-) and wild-type (OPN+/+) mice by unilateral ureteral ligation. Tissue was analyzed for macrophages (ED-1), types I and IV collagen deposition, TGF-beta expression, and for tubular and interstitial cell apoptosis. RESULTS: Obstructed kidneys from both OPN-/- and OPN+/+ mice developed hydronephrosis, tubular atrophy, interstitial inflammation and fibrosis. OPN was absent in OPN-/- kidneys but was increased in obstructed OPN+/+ kidneys. Macrophage influx, measured by computer-assisted quantitative immunostaining, was less in OPN-/- mice compared to OPN+/+ mice at day 4 (threefold, P < 0.02), day 7 (fivefold, P < 0.02), but not at day 14. Interstitial deposition of types I and IV collagen were also two- to fourfold less in obstructed OPN-/- kidneys (P < 0.02). There was also a reduction of TGF-beta mRNA expression in the interstitium at day 7 (by in situ hybridization) and a near significant 34% reduction in cortical TGF-beta activity (P = 0.06) compared to obstructed OPN+/+ kidneys at day 14. Obstructed kidneys from OPN-/- mice also had more interstitial and tubular apoptotic cells (TUNEL assay) compared to obstructed OPN+/+ mice at all time points. The ability of OPN to act as a cell survival factor was also documented by showing that the apoptosis of serum-starved NRK52E renal epithelial cells was markedly enhanced in the presence of neutralizing anti-OPN antibody. CONCLUSION: OPN mediates early interstitial macrophage influx and interstitial fibrosis in unilateral ureteral obstruction. OPN may also function as a survival factor for renal tubulointerstitial cells.     

Mizoribine ameliorates the tubulointerstitial fibrosis of obstructive nephropathy

Mizoribine has been shown to possess an immunosuppressive action that inhibits the proliferation of lymphocytes selectively by interfering with inosine monophosphate dehydrogenase. Recent studies have demonstrated that mizoribine improves renal tubulointerstitial fibrosis in the rat model of unilateral ureteral obstruction (UUO) by inhibiting the infiltration of macrophages. We, therefore, examined the dose dependency of the suppressive effect of mizoribine on the infiltration of interstitial macrophages and T lymphocytes and the interstitial volume in UUO-treated kidneys. Furthermore, we investigated the expression of osteopontin (OPN), known to be a chemoattractant protein for macrophages, in the renal cortex. In rats with UUO, the interstitial volume was markedly expanded, and macrophage and T lymphocyte infiltration in the interstitium and the expression of OPN in the cortical tubules were greatly increased. Treatment with mizoribine ameliorated the increase in interstitial volume induced by UUO. Interstitial infiltration of macrophages and T lymphocytes was dose dependently suppressed by mizoribine, and the decreased macrophage infiltration was correlated with inhibition of tubular OPN expression. These results suggest that mizoribine has a beneficial effect on several steps contributing to the progression of tubulointerstitial fibrosis caused by obstruction of the ureter.     

狼疮肾炎患者尿蛋白通过p38丝裂素活化蛋白激酶信号途径刺激近端肾小管上皮细胞上调表达骨调素

目的探讨p38丝裂素活化蛋白激酶(MAPK)信号通路在狼疮肾炎(LN)尿蛋白介导近端肾小管上皮细胞(HK-2)表达骨调素(DPN)中的作用。方法收集狼疮肾炎患者24h的尿液提纯总蛋白，体外刺激HK-2细胞，分别用逆转录-聚合酶链式反应(RT-PCR)和Western印迹法观察应用p38MAPK特异性阻断剂SB203580对。HK-2细胞表达OPN mRNA及蛋白的影响：免疫荧光法检测OPN及其受体CD44在细胞中的表达。结果狼疮肾炎患者尿蛋白可刺激HK-2细胞OPN mRNA及蛋白上调表达，并呈时间和浓度依赖性，而SB203580可明显抑制这一作用。结论狼疮肾炎尿蛋白可通过p38MAPK途径刺激HK-2细胞OPN mRNA和蛋白上调表达。     

Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy

Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. BACKGROUND: Proteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. However, most studies on this subject have been performed in experimental models, and the experience in human kidney biopsies has been scarce. We analyzed the tissue sections of patients with idiopathic membranous nephropathy (IMN), a noninflammatory glomerular disease that may follow a progressive disease with heavy persistent proteinuria, interstitial cell infiltration, and decline of renal function. METHODS: Paraffin-embedded biopsy specimens from 25 patients with IMN (13 progressive and 12 nonprogressive) were retrospectively studied by immunohistochemistry [monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted chemokine (RANTES), osteopontin (OPN), platelet-derived growth factor-BB (PD-GF-BB)] and in situ hybridization [MCP-1, RANTES, PDGF-BB, transforming growth factor-beta1 (TGF-beta1)]. Moreover, we studied the presence of myofibroblasts, which were identified by the expression of alpha-smooth muscle actin (alpha-SMA), the monocytes/macrophages (CD68-positive cells), and T-cell infiltration (CD4+ and CD8+ cells). All of the patients were nephrotic and without treatment at time of the biopsy. RESULTS: A strong up-regulation of MCP-1, RANTES, and OPN expression was observed, mainly in tubular epithelial cells, with a significant major intensity in the progressive IMN patients. A strong correlation between the mRNA expression and the corresponding protein was noted. The presence of these chemokines and OPN was associated with interstitial cell infiltration. TGF-beta and PDGF were also up-regulated, mainly in tubular epithelial cells, with a stronger expression in the progressive IMN, and an association with the presence of myofibroblasts was found. CONCLUSIONS: Patients with severe proteinuria and progressive IMN have an overexpression in tubular epithelial cells of the chemokines MCP-1, RANTES, and OPN and the profibrogenic cytokines PDGF-BB and TGF-beta. Because this up-regulation was associated with an interstitial accumulation of mononuclear cells and an increase in myofibroblastic activity, it is suggested that those mediators are potential predictors of progression in IMN. Finally, based on experimental data and the findings of this article, we speculate that severe proteinuria is the main factor responsible for the up-regulation of these factors in tubular epithelial cells.     

Macrophage colony-stimulating factor expression and macrophage accumulation in renal allograft rejection

BACKGROUND: Studies of infiltrating cells from acutely rejecting renal allografts show that a high proportion of these cells are macrophages, and early macrophage infiltration is a poor prognostic sign for transplant survival. Macrophage colony-stimulating factor (M-CSF), produced by tubular and mesangial cells, has been associated with macrophage infiltration and proliferation in experimental and human kidney diseases. We investigated the expression of M-CSF in a model of acute rejection. METHODS: Lewis rats underwent bilateral nephrectomies and received an orthotopic Dark Agouti allograft or Lewis isograft. Animals received cyclosporine (10 mg/kg/day) from day 0 to day 3 and were killed at days 4, 8, or 14 after transplantation. Macrophages (ED1+) and T cells (W3-13+) were identified by immunohistochemistry, and M-CSF expression was identified by Northern blotting and in situ hybridization. RESULTS: Isografts had normal renal function without histological evidence of rejection. Allografts exhibited a moderate infiltrate at day 4 but progressed to severe rejection at day 14, with elevated serum creatinine level and severe tubulointerstitial damage. Macrophages and T cells were present in equal proportion in the infiltrate at day 4. At day 14, the number of macrophages increased fivefold (2580/mm2), although T cells were unchanged (380/mm2). Proliferating macrophages (ED1+, BrdU+) increased from day 4 (4%) to day 14 (10%). M-CSF mRNA expression was strongly up-regulated in allografts compared with isografts and normal rat. In situ hybridization demonstrated M-CSF expression by resident and infiltrating cells. Renal tubular expression was minimally increased at day 4 but strongly up-regulated at day 14 (more than 50% of tubules positive), particularly in areas of tubular damage. Tubular M-CSF expression colocalized with areas of intense macrophage infiltration and proliferation. Serial sections with double labeling demonstrated that T cells were the dominant source of M-CSF at day 4, yet later in the rejection (day 14) the predominant sites of production were both renal tubular cells and interstitial macrophages. CONCLUSIONS: Renal production of M-CSF by graft-infiltrating (macrophages and T lymphocytes) and resident (tubular) cells was up-regulated during acute rejection. M-CSF promotes macrophage recruitment and proliferation and may thereby play a pathogenic role in acute rejection. The kinetics of M-CSF production during acute rejection suggest that local macrophage proliferation may be initiated by T cells and perpetuated by both renal tubular and autocrine release.     

Induction of MIF synthesis and secretion by tubular epithelial cells: a novel action of angiotensin II

BACKGROUND: Angiotensin II (Ang II) plays an important role in the development of renal injury through its vasoactive and proinflammatory activities. We investigated whether some of the effects of Ang II could be mediated through the production of macrophage migration inhibitory factor (MIF). METHODS: Groups of rats underwent sham surgery (sham), subtotal nephrectomy (STNx), or STNx plus treatment with irbesartan. Renal tissue was examined 12 weeks postsurgery for MIF mRNA expression and leukocyte accumulation. To determine whether Ang II had a direct effect on MIF production, mRNA synthesis and protein secretion were examined in proximal tubular epithelial (NRK52E and MCT) cell lines. RESULTS: MIF mRNA was strongly expressed in 5.4%+/- 1.1% (mean +/- SD) of cortical tubules of sham-operated rats. This was significantly up-regulated in STNx rats (44.9%+/- 22.6%) and was abrogated by administration of irbesartan (2.8%+/- 2.4%). STNx resulted in significant glomerular and interstitial accumulation of macrophages and T cells, which correlated with glomerular and tubular MIF mRNA expression, respectively. In vitro studies of tubular epithelial cells revealed that Ang II caused a twofold increase in MIF mRNA expression in NRK52E and MCT cells, which was abrogated by irbesartan. In addition, Ang II induced a rapid release of 50% of MIF protein from NRK52E cells within 20 minutes. CONCLUSION: This study has demonstrated that Ang II up-regulates MIF mRNA production and MIF protein secretion by tubular epithelial cells. Ang II may promote accumulation and activation of interstitial leukocytes via induction of MIF synthesis and secretion in renal tubular epithelial cells. This may be an important mechanism by which Ang II mediates renal injury.     

Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice

BACKGROUND: Osteopontin (OPN) is a phosphoprotein that is up-regulated in several experimental models of renal disease, including ischemia/reperfusion injury. OPN has been described as a macrophage chemoattractant, may serve as a survival factor for tubular cells, and is implicated in the development of tubulointerstitial fibrosis. However, the precise role of this protein in renal pathophysiology remains unclear. METHODS: OPN knockout and wild-type mice were subjected to 30 minutes of warm renal ischemia combined with a contralateral nephrectomy, and sacrificed at six different time points, ranging from 12 hours to seven days after reperfusion. Besides functional and morphological parameters of postischemic acute renal failure (ARF), macrophage infiltration, apoptosis and expression of collagen types I and IV were investigated. RESULTS: Postischemic ARF in OPN knockouts and wild-types showed a similar course and severity, without significant differences in either functional or morphological disease parameters. However, macrophage infiltration was significantly diminished in OPN knockouts after five and seven days, in cortex as well as in the outer stripe of the outer medulla (OSOM). Furthermore, OPN knockout mice showed significantly enhanced apoptosis in the injury phase and significantly less collagen I and IV expression in the regeneration phase of postischemic ARF. CONCLUSIONS: There was no influence of OPN protein on the severity or course of functional impairment or morphological injury in the first seven days after an ischemic insult to the kidney. However, our results demonstrate that OPN favors macrophage recruitment to the postischemic kidney, inhibits apoptosis, and stimulates the development of renal fibrosis after an acute ischemic insult.