Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct
Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct
复制标题
DOI：
10.1152/ajprenal.00383.2005
复制
发表时间：
2006-07-01
影响因子：
4.2
通讯作者：
Nielsen, Soren
中科院分区：
文献类型：
--
作者：
Christensen, Birgitte Monster;Kim, Young-Hee;Nielsen, Soren
为了研究这种分数变化多早开始，细胞的起源和变化背后的可能机制，我们在经历不同持续时间的Li治疗的大鼠中进行了时间过程研究（即，4、10和15天）。在Li治疗的第4天已经观察到尿量增加，AQP 2水平降低，尽管没有统计学显著性。在第10天和第15天，观察到显著的多尿和AQP 2表达下调。在第10天，H+-ATP酶阳性细胞的密度增加，在IMCD的锂处理的大鼠，这是在第15天进一步明显。一些H（+）ATP酶阳性细胞没有与Cl-/HCO 3-交换剂AE 1共染色，表明它们没有完全分化为A型IC。通过H+-ATP酶和增殖细胞核抗原（PCNA）或AQP 4和PCNA的双标记，我们发现，增殖主要发生在近端IMCD细胞在第4天，它增加了对中间部分的IMCD响应延长锂处理。PCNA阳性细胞多为AQP 4阳性，H+-ATPase阴性。H+-ATP酶、AQP 4和PCNA的三重标记显示一个细胞亚群对所有三种蛋白均呈阴性或仅对PCNA呈阳性。相反，4周的恢复期后，4周的锂治疗逆转增强的增殖率的控制水平。总之，锂诱导的嵌入细胞密度的增加与IM-1和IM-2中主细胞的高增殖率相关，而不是预期的嵌入细胞的选择性增殖。这可能有助于Li治疗后集合管的重塑。
To study how early this fractional change starts, the origin of the cells and the possible mechanism behind the changes, we did time course studies in rats subjected to different durations of Li treatment (i.e., for 4, 10, and 15 days). Increased urine output was already observed at day 4 of Li treatment with decreased AQP2 levels although not statistically significant. At days 10 and 15, both a significant polyuria and down-regulation in AQP2 expression were observed. At day 10, the density of H+-ATPase-positive cells was increased in the IMCD of Li-treated rats and this was further pronounced at day 15. Some of the H(+)ATPase-positive cells did not costain with Cl-/HCO3- exchanger AE1, indicating that they were not fully differentiated to type A IC. By double labeling for either H+-ATPase and proliferating-cell nuclear antigen ( PCNA) or for AQP4 and PCNA, we found that proliferation mainly occurred in proximal IMCD cells at day 4 and it increased toward the middle part of the IMCD in response to prolonged Li treatment. Most cells expressing PCNA were stained with AQP4 but not with H+-ATPase. Triple-labeling for H+-ATPase, AQP4, and PCNA showed a subset of cells negative for all three proteins or only positive for PCNA. In contrast, a 4-wk recovery period after 4 wk of Li treatment reversed the enhanced proliferative rate to the control levels. In conclusion, the Li-induced increase in the density of intercalated cells is associated with a high proliferative rate of principal cells in the IM-1 and IM-2 rather than a selective proliferation of intercalated cells as expected. This is likely to contribute to the remodeling of the collecting duct after Li treatment.