Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Zhao, Hailing; Li, Xin; Zhao, Tingting; Zhang, Haojun; Yan, Meihua; Dong, Xi; Chen, Pengmin; Ma, Liang; Li, Ping

doi:10.1371/journal.pone.0171475

Cited by 17 publications

(21 citation statements)

References 24 publications

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“…The cells were divided into the following groups: the OA group and the PA group, which were grown with 50 μM oleic acid and 50 μM sodium palmitate, respectively. The PA+TSF 250 and PA+TSF 500 groups were treated with 50 μM sodium palmitate + 250 μg/mL TSF and 50 μM sodium palmitate + 500 μg/mL TSF, respectively (Zhao et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

“…The degree of glomerulosclerosis was calculated by the percentage of extracellular matrix (ECM) deposition and mesangial expansion and evaluated at 400X power in 20 cortical fields. The mesangial matrix was scored as follows: 1, <10%; 2, 10–25%; 3, 26–50%; 4, 51–75%; 5, 76–95%; 6, >95% (Zhao et al, 2017 ). The renal sections (8 μm) of fixed frozen mouse kidneys were prepared for Oil Red O and filipin cholesterol staining.…”

Section: Methodsmentioning

confidence: 99%

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Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice

et al. 2018

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The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro. In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice

et al. 2018

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“…A recent prospective, multicenter, double-blind, randomized, controlled study has demonstrated the significant benefit of TSF in decreasing proteinuria and improving estimated glomerular filtration rate in DKD patients compared with placebo [ 12 ]. Further studies indicate TSF may attenuate DKD by inhibiting zinc finger and BTB domain containing 16 (ZBTB16/PLZF) expression [ 13 ], transforming growth factor beta (TGF-β)/SMAD family member 3 (Smad3)/nuclear factor kappa B subunit (NF-κB) signaling pathways [ 14 ], and activating Janus kinase (JAK)/signal transducer and activator of transcription (STAT)/suppressor of cytokine signaling (SOCS) signaling pathway [ 15 ]. However, the mechanism of TSF in DKD treatment remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…The goal of this study was to further explore the molecular mechanisms of TSF treatment for DKD by collecting microarray dataset GSE90842 from the National Center of Biotechnology Information Gene Expression Omnibus (NCBI GEO) public database [ 13 ] and analyzing it by a series of bioinformatics software. Compared with the study of Zhao et al [ 13 ], a non-strict threshold (P<0.05 and |logFC (fold change) | >0.1 vs. |logFC| >0.5) was selected to obtain more differentially-expressed genes (DEGs), and DEGs were run between the 2 groups by t test but not among the 3 groups by one-way ANOVA. The crucial DEGs were subsequently identified by construction of a protein and protein interaction (PPI) network and module analysis.…”

Section: Introductionmentioning

confidence: 99%

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Tangshen Formula Treatment for Diabetic Kidney Disease by Inhibiting Racgap1-stata5-Mediated Cell Proliferation and Restoring miR-669j-Arntl-Related Circadian Rhythm

Wang

Zhao

et al. 2018

Med Sci Monit

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BackgroundThe aim of this study was to investigate the underlying mechanisms of Tangshen formula (TSF) for treatment of diabetic kidney disease (DKD).Material/MethodsMicroarray dataset GSE90842 was collected from the Gene Expression Omnibus database, including renal cortical tissues from normal control (NC), DKD, and DKD mice given TSF for 12 weeks (TSF) (n=3). Differentially-expressed genes (DEGs) were identified using LIMMA method. A protein-protein interaction (PPI) network was constructed using data from the STRING database followed by module analysis. The Mirwalk2 database was used to predict the underlying miRNAs of DEGs. Function enrichment analysis was performed using the DAVID tool.ResultsA total of 2277 and 2182 genes were identified as DEGs between DKD and NC or TSF groups, respectively. After overlap, 373 DEGs were considered as common in 2 comparison groups. Function enrichment indicated common DEGs were related to cell proliferation (Asf1b, anti-silencing function 1B histone chaperone; Anln, anillin, actin-binding protein; Racgap1, Rac GTPase activating protein 1; and Stat5, signal transducer and activator of transcription 5) and circadian rhythm (Arntl, aryl hydrocarbon receptor nuclear translocator-like). Racgap1 was considered as a hub gene in the PPI network because it could interact with Asf1b, Anln, and Stat5. Arntl was regulated by miR-669j in the miRNA-DEGs network and this miRNA was also a DEG in 2 comparisons.ConclusionsTSF may be effective for DKD by inhibiting Racgap1-stata5-mediated cell proliferation and restoring miR-669j-Arntl-related circadian rhythm.

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The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome‐mediated autophagy in insulin‐resistant rats

Thongnak

Pengrattanachot

Promsan

et al. 2021

J Biochem & Molecular Tox

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Long-term use of a high-fat diet with high-fructose (HFF) intake could promote insulin resistance and induce lipid accumulation leading to kidney injury possibly via impairment of the autophagy process and enhancement of the inflammasome pathway. We investigated whether dapagliflozin as a monotherapy or combined with atorvastatin could restore kidney autophagy impairment and reduce inflammasome activation associated with kidney injury induced by HFF consumption. Male Wistar rats were given an HFF for 16 weeks and then treated with dapagliflozin with or without atorvastatin for 4 weeks. Impaired glucose tolerance, dyslipidemia, renal lipid accumulation along with impaired renal autophagy and activated inflammasome pathway promoted renal injury were exhibited in HFF rats. Dapagliflozin with or without atorvastatin treatment could partially restore disrupted metabolic parameters and reduce kidney injury.In particular, the combination treatment group showed significant amelioration of inflammasome activation and autophagy impairment. In conclusion, the combination therapy of dapagliflozin and atorvastatin has a positive effect on renal injury associated with autophagy and inflammasome activation induced by HFF in insulin-resistant rats. This study is the first report demonstrating the underlying mechanism associated with a combination treatment of dapagliflozin and atorvastatin on autophagy and inflammasome pathways in an insulinresistant condition. Therefore, dapagliflozin in combination with atorvastatin may be a further preventive or therapeutic strategy for chronic kidney disease in an insulin-resistant or diabetic condition.

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Tangshen formula attenuates diabetic renal injuries by upregulating autophagy via inhibition of PLZF expression

Cited by 17 publications

References 24 publications

Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice

Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice

Tangshen Formula Treatment for Diabetic Kidney Disease by Inhibiting Racgap1-stata5-Mediated Cell Proliferation and Restoring miR-669j-Arntl-Related Circadian Rhythm

The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome‐mediated autophagy in insulin‐resistant rats

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