| First Author | Zeng H | Year | 2020 |
| Journal | Inflamm Res | Volume | 69 |
| Issue | 12 | Pages | 1215-1234 |
| PubMed ID | 33044562 | Mgi Jnum | J:297835 |
| Mgi Id | MGI:6479315 | Doi | 10.1007/s00011-020-01411-4 |
| Citation | Zeng H, et al. (2020) TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy. Inflamm Res 69(12):1215-1234 |
| abstractText | OBJECTIVE AND DESIGN: Macrophages exhibit strong phenotypic plasticity and can mediate renal inflammation by polarizing into an M1 phenotype. They play a pivotal role in diabetic nephropathy (DN). Here, we have investigated the regulatory role of transforming growth factor beta-activated kinase 1-binding protein 1 (TAB1) in glycolysis and activation of macrophages during DN. METHODS: TAB1 was inhibited using siRNA in high glucose (HG)-stimulated bone marrow-derived macrophages (BMMs) and lentiviral vector-mediated TAB1 knockdown was used in streptozotocin (STZ)-induced diabetic mice. Western blotting, flow cytometry, qRT-PCR, ELISA, PAS staining and immunohistochemical staining were used for assessment of TAB1/nuclear factor-kappaB (NF-kappaB)/hypoxia-inducible factor-1alpha (HIF-1alpha), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. RESULTS: We found that TAB1/NF-kappaB/HIF-1alpha, iNOS and glycolysis were up-regulated in BMMs under HG conditions, leading to release of further inflammatory factors, Downregulation of TAB1 could inhibit glycolysis/polarization of macrophages and inflammation in vivo and in vitro. Furthermore, albuminuria, the tubulointerstitial damage index and glomerular mesangial expansion index of STZ-induced diabetic nephropathy mice were decreased by TAB1 knockdown. CONCLUSIONS: Our results suggest that the TAB1/NF-kappaB/HIF-1alpha signaling pathway regulates glycolysis and activation of macrophages in DN. |
