FOXO1 Overexpression Attenuates Tubulointerstitial Fibrosis and Apoptosis in Diabetic Kidneys by Ameliorating Oxidative Injury via TXNIP-TRX

Ji, Linlin; Wang, Qingzhu; Huang, Fengjuan; An, Tingting; Guo, Feng; Zhao, Yanyan; Liu, Yang; He, Yanyan; Song, Yi; Qin, Guijun

doi:10.1155/2019/3286928

Cited by 61 publications

(52 citation statements)

References 31 publications

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“…It can regulate FOXO1 through deacetylation, promote its expression and enhance its transcriptional activity . FOXO1 can reduce the damage of oxygen free radicals to kidneys by inducing autophagy . Our previous studies have shown that metformin could induce Sirt1‐FoxO1 autophagy signal axis, up‐regulate autophagy level, and inhibit cell proliferation, extracellular matrix and inflammatory factor secretion in glomerular mesangial cells induced by high glucose …”

Section: Introductionmentioning

confidence: 99%

“…11 FOXO1 can reduce the damage of oxygen free radicals to kidneys by inducing autophagy. 12 Our previous studies have shown that metformin could induce Sirt1-FoxO1 autophagy signal axis, up-regulate autophagy level, and inhibit cell proliferation, extracellular matrix and inflammatory factor secretion in glomerular mesangial cells induced by high glucose. 13 In this study, we used a high-fat diet combined with streptozotocin (STZ) to establish diabetic rat model, and observed whether metformin exerted renal protective effect by regulating autophagy mediated by the Sirt11-FoxO1 signalling pathway in DN rats.…”

mentioning

confidence: 96%

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Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end‐stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high‐fat feeding combined with intraperitoneal injection of streptozotocin. Their changes of renal function, oxidative stress, histopathology and structure, and autophagy were observed after 8 weeks of metformin treatment at different dose. Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through the Sirt1/FoxO1 autophagic signalling pathway. The results showed that metformin could protect renal function by up‐regulating autophagy level, alleviating oxidative stress level of renal tissue and pathological and structural changes of glomeruli, and inhibiting the expression of extracellular matrix. Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis. So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signalling pathway and inducing renal autophagy.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 96%

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Liu

et al. 2020

Clin Exp Pharma Physio

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“…In the present study, oral administration of Bak 1) reduced the mortality rate and improved the neurological function of animals after SAH, 2) attenuated disruption to the BBB and brain edema caused by SAH, 3) reduced the superoxide production, alleviated oxidative stress, and protected the mitochondrial ultrastructure during EBI, 4) attenuated SAH-induced cellular apoptosis and neuron damage, and 5) regulated the protein levels of Trx and TXNIP and the phosphorylation of AMPK. Moreover, both PX-12, a selective Trx inhibitor (Ji et al, 2019), and CC, a selective AMPK inhibitor (Oliveira et al, 2012;Guo et al, 2018), reversed the protective effects of Bak. To summarize, the present study confirmed that Bak can inhibit oxidative stress, attenuate cellular apoptosis, and ameliorate BBB disruption via regulating the protein level of Trx and the activity of AMPK after SAH ( Figure 6).…”

Section: Discussionmentioning

confidence: 95%

“…and oxidative stress (Ji et al, 2019). Trx2, the main ROSscavenging enzyme in mitochondria, balances ROS levels and maintains mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Liu

Guo

et al. 2020

Front. Pharmacol.

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Subarachnoid hemorrhage (SAH) is a fatal cerebrovascular condition with complex pathophysiology that reduces brain perfusion and causes cerebral functional impairments. An increasing number of studies indicate that early brain injury (EBI), which occurs within the first 72 h of SAH, plays a crucial role in the poor prognosis of SAH. Bakuchiol (Bak) has been demonstrated to have multiorgan protective effects owing to its antioxidative and anti-inflammatory properties. The present study was designed to investigate the effects of Bak on EBI after SAH and its underlying mechanisms. In this study, 428 adult male C57BL/6J mice weighing 20 to 25 g were observed to investigate the effects of Bak administration in an SAH animal model. The neurological function and brain edema were assessed. Content of MDA/3-NT/8-OHdG/superoxide anion and the activity of SOD and GSH-Px were tested. The function of the blood-brain barrier (BBB) and the protein levels of claudin-5, occludin, zonula occludens-1, and matrix metalloproteinase-9 were observed. TUNEL staining and Fluoro-Jade C staining were conducted to evaluate the death of neurons. Ultrastructural changes of the neurons were observed under the transmission electron microscope. Finally, the roles of Trx, TXNIP, and AMPK in the protective effect of Bak were investigated. The data showed that Bak administration 1) increased the survival rate and alleviated neurological functional deficits; 2) alleviated BBB disruption and brain edema; 3) attenuated oxidative stress by reducing reactive oxygen species, MDA, 3-NT, 8-OHdG, gp91 phox , and 4-HNE; increased the activities of SOD and GSH-Px; and alleviated the damage to the ultrastructure of mitochondria; 4) inhibited cellular apoptosis by regulating the protein levels of Bcl-2, Bax, and cleaved caspase-3; and 5) upregulated the protein levels of Trx1 as well as the phosphorylation of AMPK and downregulated the protein levels of TXNIP. Moreover, the protective effects of Bak were partially reversed by PX-12 and compound C. To summarize, Bak attenuates EBI after SAH by alleviating BBB disruption, oxidative

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“…Forkhead box transcription factors are required for normal tissue specification, differentiation, maintenance, and function [34][35][36]. Foxp1, a newly discovered member of the forkhead box family, plays key roles in progression of several diseases including diabetes and in processes such as fibrosis and apoptosis [37]. In our study, we found that HS loading significantly reduced the expression of Foxp1 in the renal tissues of Dahl-S rats at both mRNA and protein level, while treatment with reCREG restored Foxp1 expression in renal tissues.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Cellular Repressor of E1A-Stimulated Genes Protects against Renal Fibrosis in Dahl Salt-Sensitive Rats

Liu¹,

Song²,

Tian³

et al. 2020

Am J Nephrol

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Background: Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that attenuates angiotensin II-induced hypertension, alleviates myocardial fibrosis, and improves heart function. However, the role of CREG in high-salt (HS) diet-induced hypertensive nephropathy is unclear. Methods: To determine the effects and molecular mechanisms of CREG in HS diet-induced hypertensive nephropathy, we established a hypertensive nephropathy animal model in Dahl salt-sensitive (SS) rats fed a HS diet (8% NaCl, n = 20) for 8 weeks. At week 4 of HS loading, these rats were administered recombinant CREG (reCREG; 35 µg/kg·day, n = 5) and saline (n = 5) via subcutaneously implanted pumps and were also administered the vasodilator hydralazine (20 mg/kg·day, n = 5) in drinking water. We used hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemical labeling, western blotting, RT-PCR, and Tunel staining to determine the signaling pathways of CREG in HS diet-induced hypertensive nephropathy. Results: After 8 weeks of HS intake, the Dahl SS rats developed renal dys-function and severe renal fibrosis associated with reductions of 78 and 67% in CREG expression, respectively, at both mRNA and protein levels in the kidney. Administration of reC-REG improved renal function and relieved renal fibrosis. Administration of CREG also inhibited monocyte infiltration and reduced apoptosis in the kidney cells. CREG overexpression upregulated forkhead box P1 expression and inhibited the transforming growth factor-β1 signaling pathway. Conclusion: Our study shows that CREG protected the kidney against HS-diet-induced renal damage and provides new insights into the mechanisms underlying kidney injury.

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FOXO1 Overexpression Attenuates Tubulointerstitial Fibrosis and Apoptosis in Diabetic Kidneys by Ameliorating Oxidative Injury via TXNIP-TRX

Cited by 61 publications

References 31 publications

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Metformin alleviates renal injury in diabetic rats by inducing Sirt1/FoxO1 autophagic signal axis

Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Recombinant Cellular Repressor of E1A-Stimulated Genes Protects against Renal Fibrosis in Dahl Salt-Sensitive Rats

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