Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, PR China.
Biochem Biophys Res Commun. 2012 May 18;421(4):750-6. doi: 10.1016/j.bbrc.2012.04.075. Epub 2012 Apr 25.
There is increasing evidence that mesangial cells are important targets of chronic hypoxia injury. Impaired Ca(2+) signaling has been found in mesangial cells (MCs) subjected to chronic hypoxia. However, the mechanisms underlying this phenomenon have not yet been defined. In the present study, we found that chronic hypoxia enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) entry, and TRPC6 knockdown inhibited the chronic hypoxia-induced increase in [Ca(2+)]i, suggesting that TRPC6-mediated Ca(2+) entry is responsible for the elevated [Ca(2+)]i induced by chronic hypoxia in MCs. In addition, TRPC6 knockdown attenuated chronic hypoxia-induced actin assembly and actin reorganization. We concluded that the upregulation of TRPC6 is involved in the Ca(2+) signaling and actin assembly in human MCs after chronic hypoxia. These findings provide new insight into the mechanisms underlying the cellular response of MCs to hypoxia.
越来越多的证据表明，系膜细胞是慢性缺氧损伤的重要靶标。在慢性缺氧条件下的系膜细胞（MC）中发现了受损的 Ca（2+）信号。然而，这一现象的机制尚未确定。在本研究中，我们发现慢性缺氧增强了 TRPC6 的表达和 TRPC6 依赖性 Ca（2+）内流，而 TRPC6 敲低抑制了慢性缺氧诱导的[Ca（2+）]i 增加，表明 TRPC6 介导的 Ca（2+）内流是导致 MC 中慢性缺氧诱导的[Ca（2+）]i 升高的原因。此外，TRPC6 敲低可减轻慢性缺氧诱导的肌动蛋白组装和肌动蛋白重排。我们得出结论，TRPC6 的上调参与了慢性缺氧后人类 MC 中的 Ca（2+）信号和肌动蛋白组装。这些发现为 MC 对缺氧的细胞反应的机制提供了新的见解。
