TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy.

ABSTRACT: 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 ?-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-?B (NF-?B)/hypoxia-inducible factor-1? (HIF-1?), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. RESULTS:We found that TAB1/NF-?B/HIF-1?, 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-?B/HIF-1? signaling pathway regulates glycolysis and activation of macrophages in DN.

SUBMITTER: Zeng H 

PROVIDER: S-EPMC7658079 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature