Department of Nephrology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
Transl Res. 2012 Jun;159(6):454-63. doi: 10.1016/j.trsl.2011.11.008. Epub 2011 Dec 27.
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 β-galactosidase (SA-β-gal) staining and an immunohistochemical analysis of p21 and p16 protein expression. The expression of type III collagen (Col III) 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-β-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 III and FN in renal interstitium in IgAN patients. A correlation analysis showed that the expressions of p16, p21, and SA-β-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.
本研究旨在探讨 IgA 肾病(IgAN)患者肾小管上皮细胞(RTEC)加速衰老与疾病进展之间的潜在相关性。共纳入 108 例不同 Lee 病理分级的 IgAN 患者,另选取 18 例肾切除患者作为对照。采用衰老相关β-半乳糖苷酶(SA-β-gal)染色和 p21、p16 蛋白表达的免疫组化分析评估细胞衰老。还评估了肾间质中Ⅲ型胶原(Col III)和纤维连接蛋白(FN)的表达以及血清总胆固醇和低密度脂蛋白(LDL)胆固醇、血清肌酐浓度(SCr)和 24 小时尿蛋白排泄量。与对照组相比,Ⅰ-Ⅱ级 IgAN 患者肾活检标本中 SA-β-gal 染色及 p16 和 p21 的表达显著增加(P<0.05)。这些衰老相关标志物的表达随疾病进展逐渐增加,与 IgAN 患者肾间质中 Col III 和 FN 的表达及肾形态学变化相关。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显著相关(P<0.05),但与患者年龄、体重指数(BMI)、LDL 胆固醇水平或 24 小时尿蛋白值无关(P>0.05)。结果表明,IgAN 患者 RTEC 表现出加速衰老的特征,与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,这提示 RTECs 的加速衰老可能导致疾病进展。