Up-regulation of hypoxia inducible Factor-1α in patients with diabetic nephropathy

Wang, J; Ye, S

doi:10.4103/njcp.njcp_495_18

Cited by 5 publications

(1 citation statement)

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“…TAB1/TAK1 can activate nuclear factor κB (NF-κB) in high glucose (HG)-induced BMMs, regulating macrophage activation [8][9][10][11][12]. Studies suggest that activation of the NF-κB signaling pathway upregulates HIF-1α activity and enhances glycolytic metabolism in an autonomous fashion, HIF-1α may be considered as a novel therapeutic target for DN [13][14][15][16]. HIF-1α has been reported to be closely involved in energy metabolism and it increases the activity of glycolytic enzymes such as hexokinase-1 (HK1), 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) and lactate dehydrogenase A (LDHA) [17,18].…”

Section: Introductionmentioning

confidence: 99%

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

Zeng

et al. 2020

Inflamm. Res.

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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.

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