| First Author | Ma Y | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1228399 | PubMed ID | 37638046 |
| Mgi Jnum | J:339689 | Mgi Id | MGI:7523410 |
| Doi | 10.3389/fimmu.2023.1228399 | Citation | Ma Y, et al. (2023) The influence of angiopoietin-like protein 3 on macrophages polarization and its effect on the podocyte EMT in diabetic nephropathy. Front Immunol 14:1228399 |
| abstractText | BACKGROUND: Podocyte injury, which involves the podocyte epithelial-mesenchymal transition (EMT) process, is a crucial factor contributing to the progression of diabetic nephropathy (DN) and proteinuria. Our study aimed to examine the protective properties of Angiopoietin-like protein 3 (Angptl3) knockout on podocyte damage and macrophage polarization in DN mice and podocytes treated with HG. Furthermore, we also sought to investigate the underlying molecular mechanism responsible for these effects. METHODS: DN was induced in B6;129S5 mice through intraperitoneal injection of 40 mg/kg of streptozotocin (STZ). Subsequently, the changes in renal function, podocyte apoptosis, inflammatory factors (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], and interleukin-1beta [IL-1beta]), IL-10, TGF-beta1, IL-1Ra, IL-10Ra, and nephrin were evaluated. Moreover, we investigated the mechanism underlying the role of Angptl3 in macrophages polarization, podocyte injury, podocyte EMT. RESULTS: Our findings revealed that Angptl3 knockout significantly attenuated STZ or HG-induced renal dysfunction and podocyte EMT. In both in vivo and in vitro studies, Angptl3 knockout led to (1) promote the transformation of M1 type macrophages into M2 type macrophages; (2) amelioration of the reduced expression of nephrin, synaptopodin, and podocin; (3) inhibition of NLRP3 inflammasome activation and release of IL-1beta; and (4) regulation of alpha-SMA expression via the macrophage polarization. (5) After HG treatment, there was an increase in pro-inflammatory factors and foot cell damage. These changes were reversed upon Angptle knockdown. CONCLUSION: Our study suggests that the knockout of Angptl3 alleviates podocyte EMT and podocyte injury by regulating macrophage polarization. |
