We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy.
- Authors
Zeng, Hanxu; Qi, Xiangming; Xu, Xingxin; Wu, Yonggui
- 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 β-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-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α), iNOS, glycolysis, inflammation and the clinical and pathological manifestations of diabetic nephropathy. Results: We found that TAB1/NF-κB/HIF-1α, 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-κB/HIF-1α signaling pathway regulates glycolysis and activation of macrophages in DN.
- Subjects
DIABETIC nephropathies; MACROPHAGE activation; DESIGN exhibitions; IMMUNOSTAINING; PHENOTYPIC plasticity; MACROPHAGE inflammatory proteins; TRANSFORMING growth factors
- Publication
Inflammation Research, 2020, Vol 69, Issue 12, p1215
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-020-01411-4