Alteration in the phenotype of macrophages in the repair of renal interstitial fibrosis in mice
Alteration in the phenotype of macrophages in the repair of renal interstitial fibrosis in mice
复制标题
DOI：
10.1111/j.1440-1797.2010.01439.x
复制
发表时间：
2011-07-01
期刊：
影响因子：
2.5
通讯作者：
Kumagai, Hiroo
中科院分区：
文献类型：
--
作者：
Kushiyama, Taketoshi;Oda, Takashi;Kumagai, Hiroo
目的：肾间质纤维化是决定慢性肾脏病长期预后的最终共同途径，但其修复过程却鲜为人知。由于最近的报道表明M2型巨噬细胞在多种组织的修复中发挥着重要作用，因此本研究在分析单侧输尿管梗阻（UUO）诱导的肾纤维化解除后小鼠肾脏发生的组织学变化时，特别关注浸润巨噬细胞的表型。方法：使用血管造影剂将雄性小鼠的左侧输尿管梗阻10天。 夹子取出后，或者在肾脏恢复 3、7 或 21 天后，取出肾脏进行分析。结果：天狼星红染色评估的间质纤维化随着释放后时间的推移而减少，这种减少与 α-平滑肌肌动蛋白阳性间质面积的减少相平行。通过 F4/80 染色评估的巨噬细胞浸润也从第 3 天开始显着减少。相比之下，实时逆转录聚合酶链反应显示，巨噬细胞清道夫受体 (CD204) 和甘露糖受体 (CD206) 的 mRNA 与 CD68（一般巨噬细胞标记物）的比率在第 7 天显着更高，这两种受体均优先在 M2 巨噬细胞上表达 结论：虽然UUO释放后浸润的肌成纤维细胞和巨噬细胞总数减少，但表达CD204和CD206的巨噬细胞比例增加，提示M2型巨噬细胞在肾纤维化修复中发挥重要作用。
Aim: Renal interstitial fibrosis is the final common pathway determining long-term prognosis of chronic kidney diseases, but its repair process is scarcely understood. Because recent reports indicate that M2 macrophages play important roles in the repair of various tissues, special attention was paid to the phenotypes of infiltrating macrophages in the present study when the histological changes occurring in mouse kidneys after the release of unilateral ureteral obstruction (UUO) inducing renal fibrosis were analyzed.Methods: The left ureter of male mice was obstructed for 10 days by using a vascular clamp, and that kidney was removed for analysis either on the day when the clamp was removed or after the kidney had been allowed to recover for 3, 7 or 21 days.Results: Interstitial fibrosis assessed by picrosirius red staining decreased with time after the release, and this decrease was paralleled by a decrease in the interstitial area positive for alpha-smooth muscle actin. Macrophage infiltration assessed by F4/80 staining also significantly decreased from day 3. In contrast, real-time reverse transcription polymerase chain reaction revealed that the ratios of mRNA for the macrophage scavenger receptor (CD204) and the mannose receptor (CD206), both of which are preferentially expressed on M2 macrophages, to CD68 (a general macrophage marker) were significantly greater on day 7 than on day 0 in the UUO-released mice.Conclusion: Although the total number of infiltrating myofibroblasts and macrophages decreased after UUO release, the ratios of macrophages expressing CD204 and CD206 increased, suggesting that M2 macrophages play an important role in the repair of renal fibrosis.