Effects of BSF on Podocyte Apoptosis via Regulating the ROS-Mediated PI3K/AKT Pathway in DN

Cui, Fang-Qiang; Wang, Yuefen; Gao, Yanbin; Meng, Yuan; Cai, Zhen; Shen, Cun; Liu, Zhiqiang; Jiang, Xin-Can; Zhao, Wenjing

doi:10.1155/2019/9512406

Cited by 26 publications

(18 citation statements)

References 29 publications

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“…The PI3K/Akt signaling pathway is widely present in eukaryotic cells and participates in many physiological and pathological processes, such as cell growth, differentiation and proliferation. Studies have shown that in some disease states, stabilizing the PI3K/Akt signaling pathway can effectively alleviate damage to podocytes and reduce the incidence of proteinuria [15][16] .In recent years, studies have found that there are functional receptors for glucocorticoids in podocytes,and glucocorticoids can directly act on podocytes to protect them [17][18][19][20] . Glucocorticoids can mediate the activation of the PI3K/Akt pathway, inhibit cell apoptosis through a variety of mechanisms, and promote cell survival.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Dexamethasone reduces podocyte injury through the PTEN-PI3K/Akt signaling pathway

rRen

Zeng

et al. 2021

Preprint

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Objective: To study the role of Akt and its downstream molecules in the PTEN-PI3K/Akt signaling pathway, namely,GSK3β and Bad, in the Dexamethasone(DEX)-mediated regulation of PAN-induced glomerular podocyte injury and to elucidate the molecular mechanism of podocyte injury regulation. Methods: Glomerular podocytes (MPC5) were cultured in vitro and divided into four groups: the control group, PTEN silencing group (siPTEN group), puromycin group (PAN group), and puromycin group + DEX group (PAN+ DEX group). The cells in each group were treated for 8h, 24h, and 48h, and then, the experiment was carried out. The cells in the control group were cultured in RPMI 1640 with 0.02% DMSO, the cells in the siPTEN group were used to construct a silencing kit, the podocytes in the PAN group were treated with puromycin (final concentration of 50μg/ml), and the podocytes in the DEX+PAN group were pretreated with 0.1μmol/L DEX followed by PAN (final concentration of 50μg/ml). An inverted phase contrast microscope was used to observe the morphological changes in the podocytes and the changes in the cell body area in each group, laser confocal microscopy was used to detect the expression and distribution of the PTEN protein, and flow cytometry was used to detect and analyze the apoptosis rate and mitochondrial membrane potential of each group of podocytes. Western blot was used to detect the expression of the PTEN, P-Akt, Akt, P-GSK3β and GSK3β proteins in each group of podocytes, and transmission electron microscopy was used to observe the changes in the morphology and structure of each group of podocytes. Results: After PAN was used to injure the podocytes, the expression of the PTEN protein decreased, the rate of apoptosis increased, and the flux of autophagy was inhibited. DEX treatment reversed the changes described above.After PAN was used to injure the podocytes, the expression of p-Ak and p-GSK3β decreased, and DEX reversed these effects on the expression of p-Akt and p-GSK3β in the podocytes. Compared with the control group, in the PAN group, the mitochondria gradually swelled and rounded, mitochondrial cristae arrangement became disordered, mitochondrial autophagy was inhibited; DEX reversed the changes described above after the PTEN gene was silenced. Conclusion: This study confirmed that PAN can inhibit podocyte autophagy and induce podocyte damage. DEX can reduce the PAN-induced suppression of podocyte autophagy, enhance podocyte autophagy, and ameliorate podocyte damage. The protective mechanism may be through the upregulation of PTEN expression, which is achieved by inhibiting the activation of the PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Dexamethasone reduces podocyte injury through the PTEN-PI3K/Akt signaling pathway

rRen

Zeng

et al. 2021

Preprint

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“…The results of metabolite analysis of the urine show that there were 287 specific metabolic biomarkers that distinguished among the YSHS, DN, and normal groups, and a total of 171 pathways were involved, and the genes were binned into diabetic nephropathy pathways like the glucagon signaling pathway, insulin secretion, insulin resistance, insulin signaling pathway, etc. There are some differences between the pathway analyzed by metabolomic study and the pathway analyzed by network pharmacology, but there are some hints that the changes are related to insulin resistance, and PI3K and Akt are key insulin signaling molecules in the body, which have significant regulatory effects on glucose and DN progression (Cui et al, 2019). It was verified in the present study that YSHS significantly inhibited the phosphorylation of PI3K/AKT/mTOR, thereby delaying the progression of DN.…”

Section: Discussionmentioning

confidence: 50%

Yishen Huashi Granules Ameliorated the Development of Diabetic Nephropathy by Reducing the Damage of Glomerular Filtration Barrier

Zhao

Li²,

Xiang

et al. 2022

Front. Pharmacol.

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Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the primary cause of end-stage renal disease. At present, renin–angiotensin–aldosterone system (RAAS) blockers have been applied as first-class drugs to restrain development of DN; however, its long-term effect is limited. Recent evidence has shown definite effects of Chinese medicine on DN. Yishen Huashi (YSHS) granule is a traditional Chinese Medicine prescription that has been used in the clinic to treat DN, but its mechanism is not understood.Methods: In the present study, both in vitro and in vivo studies were carried out. The DN model was induced by STZ in Wistar rats, and GEnC and HPC cell lines were applied in the in vitro study. Quality of YSHS was evaluated by LC-MS/MS. A metabolomic study of urine was carried out by LC-MS; influence of YSHS on composition of DN was analyzed by network pharmacology. Mechanism of the YSHS on DN was analyzed by Q-PCR, Western Blot, and multi-immunological methods.Results: We found YSHS administration significantly reduced levels of HbA1c and mALB. Histopathological analysis found that YSHS preserved integrity of glomerular filtration barrier by preserving viability of glomerular endothelial cells and podocytes, inhibiting glomerular fibrosis, reducing oxidative stress damage, and enhancing cross-talk among glomerular endothelial cells and podocytes. Network pharmacology, differential metabolite analysis, as well as intracellular pathway experimental study demonstrated that the PI3K/AKT/mTOR signaling pathway played a pivotal role in it.Conclusion: Our present findings supplied new understanding toward the mechanism of YSHS on inhibiting DN.

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“…As the main component of EH, quercetin has been proved to improve renal fibrosis and apoptosis in chronic renal failure rats, as well as reducing water retention and toxin accumulation by inhibiting the PI3k/Akt pathway through targeting PIK3R [ 53 ]. Thus, regulating the PI3K/AKT pathway in podocytes through EH may be an important potential targeted therapy for NS in the future [ 54 ]. As one of important inflammatory pathways, the TNF signaling pathway plays a central role in the regulation of different cellular events such as immunity, apoptosis, cell proliferation, and differentiation [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

Yao

Wang

Han

et al. 2022

BioMed Research International

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Objective. To explore the possible mechanisms of Ephedra herb (EH) in the treatment of nephrotic syndrome (NS) by using network pharmacology and molecular docking in this study. Methods. Active ingredients and related targets of EH were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the gene names corresponding to the proteins were found through the UniProt database. Then, target genes related to NS were screened out from GeneCards, PharmGKB, and OMIM databases. Next, the intersection targets were obtained successfully through Venn diagram, which were also seen as key target genes of EH and NS. Cytoscape 3.9.0 software was used to construct the effective “active ingredient-target” network diagram, and “drug-ingredient-target-disease (D-I-T-D)” network diagram. After that, the STRING database was used to construct a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment involved in the targets were performed by the DAVID database and ClueGO plugin in Cytoscape. Finally, AutoDockTools software was used for molecular docking to verify the binding strength between main active ingredients and key target proteins. Results. A total of 22 main active ingredients such as quercetin, kaempferol, luteolin, and naringenin were obtained, which could act on 105 targets related to NS. Through PPI network, 53 core targets such as AKT1, TNF, IL6, VEGFA, and IL1B were found, which might play a crucial role in the treatment of NS. Meanwhile, these targets were significantly involved in PI3K-Akt signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, hepatitis B, and pathways in cancer through GO and KEGG enrichment analysis. The docking results indicated that active ingredients such as kaempferol, luteolin, quercetin, and naringenin all had good binding to the target protein AKT1 or TNF. Among them, luteolin and naringenin binding with AKT1 showed the best binding energy (-6.2 kcal/mol). Conclusion. This study indicated that the potential mechanism of EH in treating NS may be related to PI3K-Akt signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway, which provided better approaches for exploring the mechanism in treating NS and new ideas for further in vivo and in vitro experimental verifications.

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Effects of BSF on Podocyte Apoptosis via Regulating the ROS-Mediated PI3K/AKT Pathway in DN

Cited by 26 publications

References 29 publications

WITHDRAWN: Dexamethasone reduces podocyte injury through the PTEN-PI3K/Akt signaling pathway

WITHDRAWN: Dexamethasone reduces podocyte injury through the PTEN-PI3K/Akt signaling pathway

Yishen Huashi Granules Ameliorated the Development of Diabetic Nephropathy by Reducing the Damage of Glomerular Filtration Barrier

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking

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