我们近期发现miR-30能通过抑制“有害”的钙-钙调磷酸酶信号通路而保护足细胞（Wu J, J Clin Invest, 2015）。然而，该通路抑制剂并不能完全消除miR-30丧失所导致的足细胞损伤，提示miR-30还抑制其它“有害”靶基因，因而miR-30的下调激活该“有害”基因并参与足细胞损伤。我们通过生物信息学分析锁定Pawr为潜在的“有害”基因。尽管足细胞中尚未任何有关Pawr的报道，但在其它细胞类型中Pawr能抑制WT1这一足细胞关键蛋白，并通过Bcl2和MAPK p38诱导凋亡。本研究中我们将 1）用体外系统验证“miR-30→Pawr→WT1/Bcl2→足细胞损伤"通路；2）用PAN-大鼠、足细胞特异的Pawr转基因和基因敲除小鼠，验证Pawr对足细胞的损伤作用；3）检测Pawr蛋白是否在肾小球病患者足细胞上调。本研究揭示的新机制有助于发展更为有效的足细胞病防治手段。

We have recently found that miR-30 protects podocytes and maintains their homeostasis via inhibiting injurious calcium-calcineurin signaling (Wu J, J Clin Invest, 2015). However, we also found that the inhibitor of calcineurin signaling FK506 or Cyclosporine does not fully reverse the injury induced by miR-30 loss, suggesting that miR-30 inhibits other harmful genes as well, and therefore when miR-30 is lost the harmful gene(s) are activated to induce podocyte injury. Through bioinformatics analysis we speculate that the gene Pawr is the most promising candidate of the harmful genes. Supportively, studies have shown in non-podocytes that Pawr inhibits WT1, a key protein for podocyte; and Pawr also induces apoptosis via Bcl2 and MAPK p38, which have been shown to mediate apoptosis in podocytes as well. To test our hypothesis, we will 1) confirm the presence of “miR-30→Pawr→WT1/Bcl2泡8→ injury" pathway in cultured podocytes, 2) confirm the injurious effect of Pawr by using PAN-treated rats, podocyte-specific Pawr transgenic and knockout mice, and 3) examine whether PAWR protein is upregulated in the podocytes of the patients with glomerular diseases. The elucidation of this novel mechanism of podocyte injury may help develop more effective treatments of podocytopathy.