Background: Our previous research revealed that the apoptosis of proximal tubular epithelial cells (PTECs) occupied a vital position in the early change of diabetic nephropathy (DN) and Bcl-interacting mediator (Bim) was the key factor to be involved in it. Whereas, Bim could also control T cell activation and play a specific regulatory role in other aspects besides inducing cell apoptosis. Changes of podocytes are classic hallmarks of the lesions of DN. Here, the study aims to investigate the specific influence of PTECs which have been damaged on the podocyte injury.
Methods: Bim expression in PTECs was modulated, and subsequently podocyte cytoskeleton was determined at different points of time (24, 48, 72 hours) by building transwell co-culture system under high glucose (40mmol/l HG).
Results: HG exposure for 48 hours induced the significant changes in podocyte cytoskeleton accompanied with high expression of Bim in PTECs. When co-cultured with PTECs, exacerbated filamentous actin (F-actin) rearrangement and markedly reduced synaptopodin level in podocytes were found compared with single cultured podocytes under HG. Gene knockdown of Bim in PTECs ameliorated above abnormalities in podocytes. Further screening for NFAT subtypes, the key downstream factors of Bim, found that NFAT2 level in PTECs was obviously decreased when suppressing Bim expression. Upregulating NFAT2 disrupted beneficial effects on podocyte F-actin arrangement which was achieved by inhibiting Bim in PTECs.
Conclusion: Our preliminary data have indicated that the apoptosis of PTECs mediates the early lesion of DN. It seemed corroborative that there exists crosstalk between PTECs and podocytes; Bim, the pivotal factor related to apoptosis of PTECs participates in the crosstalk by promoting NFAT2 activation, then contributes to injury of podocyte cytoskeleton, emphasizing the role of Bim/NFAT2 pathway in the control of early DN progression from tubular lesions to glomerular abnormalities.
C. Xu: None. X. Zhou: None. X. Shen: None. S. Jiang: None. T. Xie: None. Z. Zou: None. Q. Zhang: None. R. Zhang: None. Y. Xing: None. L. Liao: None. J. Dong: None.
National Natural Science Foundation of China (81570742, 81670757, 81770822, 81800732); Shandong Provincial Natural Science Foundation of China (ZR2017LH025); Shandong Provincial Medicine and Health Science and Technology Development Program (2017WS461)