Kidney injury molecule-1 expression in IgA nephropathy and its correlation with hypoxia and tubulointerstitial inflammation
Kidney injury molecule-1 expression in IgA nephropathy and its correlation with hypoxia and tubulointerstitial inflammation
复制标题
IgA肾病中肾损伤分子1的表达及其与缺氧、肾小管间质炎症的相关性
DOI：
10.1152/ajprenal.00331.2013
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发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Lin, Qiongzhen;Chen, Ying;Yang, Li
肾小管间质损伤在慢性肾脏病（CKD）的发生和进展中起着重要作用。在急性肾损伤和 CKD 中，肾损伤分子 (KIM)-1 在受损的近端肾小管中被诱导。然而，KIM-1 在 CKD 中的动态以及 KIM-1 表达对疾病进展的影响尚不清楚。在这里，我们的目的是确定 CKD 中肾小管 KIM-1 表达水平、肾功能和炎症之间的关联。对进行性和非进行性 IgA 肾病患者的 KIM-1 水平与临床病理参数之间的关系进行了分析。 IgA肾病患者中KIM-1表达升高，且其表达与肾功能下降显着相关。 KIM-1 在毛细血管密度降低的部位尤其明显，并且 KIM-1 阳性小管被炎症细胞浸润包围。使用体外细胞模型，我们发现细胞应激源（包括缺氧）会诱导 KIM-1 表达。在缺氧条件下培养时，表达 KIM-1 的细胞产生更多的趋化因子/细胞因子。此外，我们发现表达 KIM-1 的肾小管细胞可以通过分泌趋化因子来调节炎症细胞的免疫反应。这些数据表明，表达 KIM-1 的上皮细胞可能通过分泌趋化因子/细胞因子在慢性肾损伤期间肾小管间质炎症的发病机制中发挥作用。
Tubulointerstitial injury plays an important role in the development and progression of chronic kidney disease (CKD). Kidney injury molecule (KIM)-1 is induced in damaged proximal tubules in both acute renal injury and CKD. However, the dynamics of KIM-1 in CKD and effects of KIM-1 expression on disease progression are unknown. Here, we aimed to determine the associations between tubular KIM-1 expression levels, renal function, and inflammation in CKD. The relationships between levels of KIM-1 and clinicopathological parameters were analyzed in patients with progressive and nonprogressive IgA nephropathy. KIM-1 expression was increased in patients with IgA nephropathy, and its expression was significantly correlated with the decrease of renal function. KIM-1 was particularly evident at the site with reduced capillary density, and KIM-1-positive tubules were surrounded by infiltrates of inflammatory cells. Using in vitro cell models, we showed that cellular stressors, including hypoxia, induced KIM-1 expression. KIM-1-expressing cells produced more chemokines/cytokines when cultured under hypoxic conditions. Furthermore, we showed that tubular cells with KIM-1 expression can regulate the immune response of inflammatory cells through the secretion of chemotactic factors. These data suggest that KIM-1-expressing epithelial cells may play a role in the pathogenesis of tubulointerstitial inflammation during chronic renal injury through the secretion of chemokines/cytokines.