The Water and Salt Research Center, Aarhus University, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University Hospital-Skejby, Aarhus, Denmark.
Acta Physiol (Oxf). 2013 Oct;209(2):167-78. doi: 10.1111/apha.12135. Epub 2013 Jul 9.
In vivo, renal medullary interstitial cells (RMICs) and collecting duct principal cells (mpkCCD cells) are subjected to inflammatory, oxidative and mechanical stress as a result of unilateral ureteral obstruction (UUO). Because heat-shock protein (HSP) 27 and HSP70 are induced by cellular stresses and play a role in cytoprotection, we hypothesized that HSP27 and HSP70 are increased in rats subjected to acute UUO and in RMICs and mpkCCD cells exposed to inflammatory, oxidative or mechanical stress.
Rats were subjected to acute UUO for 6 h and 12 h. To examine the expression of HSP27, phosphorylated HSP27 (pHSP27) and HSP70 in response to inflammatory, oxidative and mechanical stress in vitro, we exposed RMICs and mpkCCD cells to interleukin 1β (IL-1β), hydrogen peroxide (H2 O2 ), and stretch stimulation over time.
The phosphorylated form of HSP27 (pHSP27) was increased in the renal inner medulla (IM) after 6-h and 12-h UUO, while HSP27 and HSP70 were unchanged. Furthermore, after 6 h and 12 h of UUO, the expression of inflammatory (IL-1β) and oxidative [haem oxygenase 1 (HO-1)] markers was induced. Exposure to inflammatory, oxidative and mechanical stress changed HSP27 and pHSP27 expression in RMICs but not in mpkCCD cells, while HSP70 was not affected by any of the stress conditions. Exposure of RMICs to oxidative and mechanical stress induced HSP27 phosphorylation via a p38-dependent mechanism.
These data demonstrate that, in response to acute UUO, different forms of cellular stresses modulate HSP27 expression and phosphorylation in RMICs. This may affect the ability of renal cells to mount an effective cytoprotective response.
在体内，由于单侧输尿管梗阻（UUO），肾髓质间质细胞（RMICs）和集合管主细胞（mpkCCD 细胞）会受到炎症、氧化和机械应激。由于热休克蛋白（HSP）27 和 HSP70 是由细胞应激诱导的，并在细胞保护中发挥作用，我们假设 HSP27 和 HSP70 在急性 UUO 大鼠和暴露于炎症、氧化或机械应激的 RMICs 和 mpkCCD 细胞中增加。
大鼠接受急性 UUO 处理 6 h 和 12 h。为了研究 HSP27、磷酸化 HSP27（pHSP27）和 HSP70 在体外对炎症、氧化和机械应激的表达，我们随时间将 RMICs 和 mpkCCD 细胞暴露于白细胞介素 1β（IL-1β）、过氧化氢（H2O2）和拉伸刺激下。
UUO 后 6 h 和 12 h，肾髓质（IM）中 HSP27 的磷酸化形式（pHSP27）增加，而 HSP27 和 HSP70 不变。此外，UUO 后 6 h 和 12 h，炎症（IL-1β）和氧化[血红素加氧酶 1（HO-1）]标志物的表达被诱导。炎症、氧化和机械应激暴露改变了 RMICs 中 HSP27 和 pHSP27 的表达，但对 mpkCCD 细胞没有影响，而 HSP70 不受任何应激条件的影响。RMICs 暴露于氧化和机械应激会通过 p38 依赖性机制诱导 HSP27 磷酸化。
这些数据表明，急性 UUO 后，不同形式的细胞应激调节 RMICs 中 HSP27 的表达和磷酸化。这可能会影响肾脏细胞产生有效细胞保护反应的能力。
