High glucose induced-macrophage activation through TGF-β-activated kinase 1 signaling pathway

Xu, Xingxin; Qi, Xiangming; Shao, Yunxia; Li, Yuanyuan; Fu, Xin; Feng, Shiyao; Wu, Yuangang

doi:10.1007/s00011-016-0948-8

Cited by 23 publications

(13 citation statements)

References 31 publications

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“…NF-κB is a recognized downstream signaling target molecule of TAB1/TAK1. After Toll-like receptor signal transduction, TAK1/TAB1 mediates NF-κB p65 nuclear entry through IKKα/β, inducing further inflammation [9]. Emerging evidence points to NF-κB control over the HIF signaling pathway and interaction between the HIF signaling pathway and the NF-κB signaling cascade [14].…”

Section: Discussionmentioning

confidence: 99%

“…Transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) is a specific protein that interacts with transforming growth factor β-activated kinase 1 (TAK1). 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].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

Zeng

et al. 2020

Inflamm. Res.

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“…The early pathological changes of DN are mainly glomerulosclerosis, renal arteriolar damage, and renal tubular degeneration; interstitial fibrosis is a prominent presentation in the late stage [22]. In this study, a type 1 diabetes mellitus mouse model was established through intraperitoneal injection of Journal of Diabetes Research STZ.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Diabetic Nephropathy in Diabetic Mice by Fasudil through Regulation of Macrophage Polarization

Xie

Lei

Ran

et al. 2020

Journal of Diabetes Research

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Inflammation and fibrosis induced by hyperglycemia are considered to play a critical role in the pathogenesis of diabetic nephropathy. As macrophage polarization may determine the severity and progression of inflammation, regulation of macrophage polarization may be an effective method to treat diabetic complications. Fasudil, a potent Rho-kinase inhibitor, reportedly exhibits anti-inflammatory activity. However, whether fasudil reduces hyperglycemia-induced diabetic nephropathy via regulation of macrophage polarization remains unclear. In this study, we investigate the effect of fasudil on diabetic nephropathy in streptozotocin-induced type 1 diabetic mice. Our data showed that fasudil significantly decreased urinary protein and serum creatinine in diabetic mice, whereas it had no effect on the body weight and blood glucose. We also found increased M1-type macrophages and related proinflammatory cytokines, adverse fibrosis in renal tissue of diabetic mice. Interestingly, treatment of diabetic mice with fasudil increased the number of M2-type macrophages and related anti-inflammatory cytokines, which attenuated renal injury in diabetic mice. Taken together, the results of this study suggest that fasudil could slow the progression of diabetic nephropathy. The possible mechanism might be associated with its induction of M2 macrophage polarization and the reduction of M1 macrophage polarization and inflammation.

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“…Studies have found that ROS, TGF-β1and NF-κBp65 are closely associated with the etiology of bronchopulmonary dysplasia. Reactive oxygen species (ROS) which are involved in the NF-κBp65 pathway, activate S6 kinase, induce phosphorylation of IκB, and dissociate NF-κBp65, thereby causing nuclear translocation and regulation of the transcriptions of TGF-β1and other factors [3]. It has been suggested that ROS may play crucial roles in lung tissue damage [4].…”

Section: Bronchopulmonarymentioning

confidence: 99%

Expression levels of reactive oxygen species, NF-κBp65 and TGF-β1 and their correlations in bronchopulmonary dysplasia in neonatal rats

Wang¹,

Sun²,

Wang³

et al. 2020

Trop. J. Pharm Res

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Purpose: To study the levels of reactive oxygen species (ROS), nuclear transcription factor-κBp65 (NF-κBp65) and TGF-1, and their correlation in bronchopulmonary dysplasia in neonatal rats.Methods: Twenty (20) pregnant rats were randomly divided into study and normal groups. Radial alveolar counts were carried out at 2, 8 and 15 days of age. The levels of ROS expression in the lung tissues of the two groups were assayed by ELISA while immunohistochemistry was used to determine the expressions of TGF-β1 and NF-κBp65 in neonatal lung tissues of the two groups. Pearson correlation test was used to analyze correlations amongst ROS, TGF-β1 and NF-κBp65 in the neonatal lung tissues.Results: At days 8 and 9 after birth, radial alveolar count was significantly lower in study rats than in control rats (p < 0.05). Expression levels of ROS, TGF-β1 and NF-κBp65 in study group were markedly raised at days 2, 4 and 8 after birth, relative to control (p < 0.05).Conclusion: The levels of ROS, TGF-β1 and NF-κBp65 in bronchopulmonary dysplasia in neonatal rats are significantly and positively correlated, and are higher than those in normal rats. This provides a scientific basis for development of drugs for bronchopulmonary dysplasia. Keywords: Neonatal rats, Bronchopulmonary dysplasia, Lung tissue, NF-κBp65, TGF-β1, Correlation

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High glucose induced-macrophage activation through TGF-β-activated kinase 1 signaling pathway

Cited by 23 publications

References 31 publications

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

TAB1 regulates glycolysis and activation of macrophages in diabetic nephropathy

Attenuation of Diabetic Nephropathy in Diabetic Mice by Fasudil through Regulation of Macrophage Polarization

Expression levels of reactive oxygen species, NF-κBp65 and TGF-β1 and their correlations in bronchopulmonary dysplasia in neonatal rats

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