Quantitative and Qualitative Urinary Cellular Patterns Correlate with Progression of Murine Glomerulonephritis
Quantitative and Qualitative Urinary Cellular Patterns Correlate with Progression of Murine Glomerulonephritis
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DOI：
10.1371/journal.pone.0016472
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发表时间：
2011-01-31
期刊：
影响因子：
3.7
通讯作者：
Kon, Yasuhiro
中科院分区：
文献类型：
--
作者：
Kimura, Junpei;Ichii, Osamu;Kon, Yasuhiro
肾脏是由许多功能肾单位和集合管(CD)组成的非再生器官。肾小球和肾小管间质损害会减少功能性肾单位的数量，引起解剖学和生理学改变，导致肾功能障碍。最近有报道称，在与肾功能恶化相关的几种病理情况下，肾单位组成细胞会掉入尿液中。我们研究了小鼠肾小球肾炎模型中尿液细胞的定量和定性模式，并阐明了细胞模式与肾脏病理的相关性。对BXSB/MPJ(BXSB；肾炎模型)和C57BL/6(B6；对照)小鼠的尿细胞学和肾脏组织病理学进行了分析。尿细胞学检查显示，BXSB小鼠的尿细胞数随肾小球肾炎的组织计量学评分和尿白蛋白的变化而变化，但与血尿素氮和肌酐水平无相关性。在BXSB尿液中检测到足细胞、远端小管和CDS的特异性标志物的表达。肾组织Wilms肿瘤1(足细胞标记物)和白介素1家族成员6(受损的DT和CD标记物)免疫阳性细胞数在补肾活血方较补肾活血方分别显著减少和增加。在炎性细胞因子和趋化因子的PCR阵列分析中，IL10、CxCl2、C3和IL1rn在BXSB肾脏中的表达相对高于B6肾脏。BXSB小鼠尿液中C3mRNA的表达水平最高。此外，C3蛋白和信使核糖核酸也定位于受损肾单位的上皮细胞。这些发现表明，肾小球上皮细胞、肾小管上皮细胞和肾小管上皮细胞滴入尿液中，这些模式与肾脏病理进展有关。我们得出结论，尿液细胞类型的评估在肾脏疾病的早期、非侵入性诊断中起着关键作用。
The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology. Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons. These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.