Inhibition of hyaluronan is protective against renal ischaemiareperfusion injury
Inhibition of hyaluronan is protective against renal ischaemiareperfusion injury
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DOI：
10.1093/ndt/gft314
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发表时间：
2013-10-01
影响因子：
6.1
通讯作者：
Caron, Nathalie
中科院分区：
文献类型：
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作者：
Colombaro, Vanessa;Decleves, Anne-Emilie;Caron, Nathalie
肾缺血再灌注损伤（IRI）是一个复杂的病理生理过程，可导致移植肾的急性肾功能衰竭和慢性功能障碍。先前证明，在IRI期间，透明质酸（HA）在皮质和外髓皮质沿着中积聚，同时其主要受体CD 44在炎性细胞和肾小管细胞上的表达增加。HA-CD 44对可能参与持续性缺血后炎症。因此，我们试图确定HA在缺血再灌注（IR）的病理生理学中的作用，通过防止其在缺血后肾脏中的积累。C57 BL/6小鼠接受含有4-甲基伞形酮（4-MU）的饮食，4-MU是一种有效的HA合成抑制剂。在治疗结束时，诱导单侧肾IR，并在IR后48小时或30天对小鼠实施安乐死。4-MU治疗14周降低了IR后48小时的血浆HA水平和肾内HA含量，以及CD 44表达、肌酸酐血症和组织病理学病变。此外，在用4-MU处理的动物中，炎症显著减弱并且增殖减少。此外，4-MU治疗的小鼠有一个显着减少的表达-SMA和胶原蛋白I型和III型，即减少肾纤维化，IR后30天与未经处理的mice相比，我们的研究结果表明，HA在IRI的发病机制中起着重要的作用，可能部分通过减少CD 44的表达。IR期间HA蓄积的抑制可保护肾功能免受缺血性损伤。
Ischaemiareperfusion injury (IRI) to the kidney is a complex pathophysiological process that leads to acute renal failure and chronic dysfunction in renal allografts. It was previously demonstrated that during IRI, hyaluronan (HA) accumulates in the cortical and external medullary interstitium along with an increased expression of its main receptor, CD44, on inflammatory and tubular cells. The HA-CD44 pair may be involved in persistent post-ischaemic inflammation. Thus, we sought to determine the role of HA in the pathophysiology of ischaemiareperfusion (IR) by preventing its accumulation in post-ischaemic kidney.C57BL/6 mice received a diet containing 4-methylumbelliferone (4-MU), a potent HA synthesis inhibitor. At the end of the treatment, unilateral renal IR was induced and mice were euthanized 48 h or 30 days post-IR.4-MU treatment for 14 weeks reduced the plasma HA level and intra-renal HA content at 48 h post-IR, as well as CD44 expression, creatininemia and histopathological lesions. Moreover, inflammation was significantly attenuated and proliferation was reduced in animals treated with 4-MU. In addition, 4-MU-treated mice had a significantly reduced expression of -SMA and collagen types I and III, i.e. less renal fibrosis, 30 days after IR compared with untreated mice.Our results demonstrate that HA plays a significant role in the pathogenesis of IRI, perhaps in part through reduced expression of CD44. The suppression of HA accumulation during IR may protect renal function against ischaemic insults.