Beijing You An Hospital, Capital Medical University, 100069, Beijing, China.
Beijing Institute of Hepatology, 100069, Beijing, China.
Cell Death Dis. 2018 Oct 9;9(10):1031. doi: 10.1038/s41419-018-1098-4.
The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGFβ and NFκB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGFβ in polycystic kidney disease and attenuate EMT in renal tubular cells. Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes through downregulating the expression and activation of TGFβ/Smad pathway in diabetic kidney diseases. The results showed that apelin in glomeruli of diabetic mice were increased and exogenous apelin inhibited the EMT of podocytes in diabetic mice, which were accompanied with the decreased expression of proteasome subunits β5i. The results from β5iKO mice confirmed that the inhibiting effects of apelin on EMT of podocytes in diabetic mice were dependent on β5i. The results from culture podocytes showed that apelin decreased the degradation of pIκB and promoted the translocation of IκB into nucleus through decreasing the expression of β5i, which would inhibit the promoting effects of NFκB on expression of TGFβ and followed by decreased activation of Smad pathway and EMT in podocytes. In conclusion, apelin might act as an EMT suppressor for podocytes to decrease the process of glomerular fibrosis in diabetic mice.
足细胞的上皮-间充质转化（EMT）已被报道参与糖尿病肾病的肾小球纤维化，这一过程受 TGFβ 和 NFκB 通路调控。脂联素是一种在糖尿病肾病中上调的脂肪细胞因子，有报道称其与多囊肾病中的 TGFβ 呈负相关，并能减轻肾小管细胞的 EMT。因此，研究假设脂联素可能通过下调糖尿病肾病中 TGFβ/Smad 通路的表达和激活来抑制足细胞的 EMT。结果表明，糖尿病小鼠肾小球中的脂联素增加，外源性脂联素抑制糖尿病小鼠足细胞的 EMT，同时伴随蛋白酶体亚基 β5i 的表达减少。β5iKO 小鼠的结果证实，脂联素抑制糖尿病小鼠足细胞 EMT 的作用依赖于β5i。培养的足细胞实验表明，脂联素通过降低β5i 的表达减少 pIκB 的降解，并促进 IκB 向核内转位，从而抑制 NFκB 对 TGFβ 表达的促进作用，随后降低 Smad 通路的激活和足细胞的 EMT。综上所述，脂联素可能作为足细胞的 EMT 抑制剂，减少糖尿病小鼠肾小球纤维化的进程。
