Laboratory of Anatomy, Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
PLoS One. 2011 Jan 31;6(1):e16472. doi: 10.1371/journal.pone.0016472.
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.
肾脏是一个由许多功能肾单位和集合管组成的非再生器官。肾小球和肾小管间质损伤会减少功能肾单位的数量，并导致解剖和生理改变，从而导致肾功能障碍。最近有报道称，在几种与肾功能恶化相关的病理情况下，肾单位组成细胞会脱落到尿液中。我们在小鼠肾小球肾炎模型中研究了尿细胞的定量和定性模式，并阐明了细胞模式与肾脏病理之间的相关性。
在 BXSB/MpJ（BXSB；肾小球肾炎模型）和 C57BL/6（B6；对照）小鼠中分析了尿细胞学和肾组织病理学。尿细胞学显示，BXSB 小鼠的尿细胞数量随肾小球肾炎和尿白蛋白的组织学评分而变化；然而，未检测到血尿素氮和肌酐水平的相关性。在 BXSB 尿液中检测到足细胞、远曲小管（DT）和 CD 的特定标志物的表达。在肾脏中，Wilms 肿瘤 1（足细胞标志物）和白细胞介素 1 家族成员 6（受损 DT 和 CD 标志物）的免疫阳性细胞在 BXSB 中分别显著减少和增加。在炎症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。特别是，在 BXSB 小鼠的尿液中检测到 C3 mRNA 的最高表达。此外，C3 蛋白和 mRNA 定位于受损肾单位的上皮细胞中。
这些发现表明肾小球、DT 和 CD 的上皮细胞脱落到尿液中，这些模式与肾脏病理进展有关。我们得出结论，评估尿细胞模式在肾脏疾病的早期、非侵入性诊断中起着关键作用。
