Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy
Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy
复制标题
DOI：
10.1016/j.trsl.2011.11.008
复制
发表时间：
2012-06-01
影响因子：
7.8
通讯作者：
Xiao, Hua-Shi
中科院分区：
文献类型：
--
作者：
Liu, Jun;Yang, Ju-Rong;Xiao, Hua-Shi
本研究的目的是确定肾小管上皮细胞（RTECs）加速衰老与免疫球蛋白A肾病（IgAN）患者疾病进展之间的潜在相关性。共有108例不同Lee病理分级的IgAN患者入组。此外，还招募了18例肾切除术患者作为对照。通过衰老相关的β -半乳糖苷酶（sa - β -gal）染色和p21和p16蛋白表达的免疫组织化学分析来评估细胞衰老。同时检测肾间质III型胶原（Col il）和纤连蛋白（FN）的表达，血清总胆固醇和低密度脂蛋白（LDL）胆固醇水平、血清肌酐浓度（SCr）和24 h尿蛋白排泄量。与对照组相比，I-II级IgAN患者肾活检标本中sa - β -gal染色和p16、p21的表达显著增加（P < 0.05）。这些衰老相关标志物的表达随着疾病的进展而逐渐增加，并与IgAN患者肾脏形态学改变和肾间质Col il和FN的表达相关。相关性分析显示，p16、p21和sa - β -gal染色的表达与血压和肾功能有显著相关性（P < 0.05），而与患者年龄、体重指数（BMI）、LDL胆固醇水平或24小时尿蛋白值无显著相关性（P < 0.05）。我们的研究结果表明，IgAN患者的RTECs表现出加速衰老的特征，这与正常衰老相关的机制无关。细胞衰老与IgAN疾病进展密切相关，这表明rtec的加速衰老可能有助于这种进展。（翻译研究2012；159:454-463）
The aim of this study is to determine the potential correlation between the accelerated senescence of renal tubular epithelial cells (RTECs) and the disease progression of patients with immunoglobulin A nephropathy (IgAN). A total of 108 IgAN patients with different Lee's pathologic grades were enrolled. Additionally, 18 patients with renal resection were recruited as controls. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) staining and an immunohistochemical analysis of p21 and p16 protein expression. The expression of type III collagen (Col Ill) and fibronectin (FN) in renal interstitium and the levels of serum total and low-density lipoprotein (LDL) cholesterol, serum creatinine concentration (SCr), and 24-h urinary protein excretion were evaluated also. SA-beta-gal staining and the expression of p16 and p21 were increased significantly in renal biopsy specimens obtained from grades I-II IgAN patients compared with controls (P < 0.05). The expression of these senescence-associated markers increased gradually with disease progression and correlated with the renal morphologic changes and the expression of Col Ill and FN in renal interstitium in IgAN patients. A correlation analysis showed that the expressions of p16, p21, and SA-beta-gal staining were associated significantly with blood pressure and renal function (P < 0.05), but not with patient age, body mass index (BMI), LDL cholesterol level, or 24-h urinary protein value (P > 0.05). Our results indicated that the RTECs in IgAN patients exhibited features of accelerated senescence, which were unrelated to mechanisms associated with normal aging. Cellular senescence was associated closely with IgAN disease progression, which suggested the accelerated senescence of RTECs may contribute to this progression. (Translational Research 2012;159:454-463)