Osteopontin expression in acute renal allograft rejection
Osteopontin expression in acute renal allograft rejection
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DOI：
10.1111/j.1523-1755.2005.00153.x
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发表时间：
2005-03-01
影响因子：
19.6
通讯作者：
Gejyo, F
中科院分区：
文献类型：
--
作者：
Alchi, B;Nishi, S;Gejyo, F
背景骨桥蛋白（OPN）是一种有效的单核细胞趋化因子，在肾脏的各种炎症状态中上调。骨桥蛋白及其表达在人肾移植排斥反应中的作用尚不清楚。我们通过免疫组织化学和原位杂交检测了急性排斥反应患者（N = 22）、无排斥反应患者（N = 9）和围手术期供体（N = 35）肾活检组织中OPN的表达及其与临床、实验室和组织病理学参数的相关性。在排斥反应活检中，研究了间质单核细胞/巨噬细胞浸润、肾小管间质细胞增殖/再生和凋亡。在大多数排斥活检中，近端肾小管上皮细胞广泛表达OPN，并且在被大量炎性细胞包围的肾小管中倾向于增强。相反，在未发生排斥反应的患者和供体活检中，近端小管的OPN表达为零或弱。OPN mRNA与其翻译蛋白共定位于肾小管上皮细胞。OPN表达与间质炎症程度呈正相关（P < 0.05），CD 68+单核细胞浸润Ki-67阳性的肾小管间质细胞数明显高于阴性（P < 0.01）（P < 0.05和P < 0.005），但不与末端脱氧核苷酸转移酶（TdT）介导的脱氧尿苷三磷酸（dUTP）缺口末端标记（TUNEL）-肾小管上皮细胞凋亡阳性。这些数据表明，肾小管上皮细胞中OPN的诱导表达可能通过介导间质单核细胞浸润和可能的肾小管再生在急性肾移植排斥反应中起致病作用。
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.