Dataset Information

Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats.

ABSTRACT:

Objective

This study aims to figure out the mechanism of astragaloside IV (AS-IV) in the protection of podocyte apoptosis in diabetic nephropathy (DN) rats.

Materials and methods

Streptozotocin (STZ) was used to induce diabetes in rats, and the diabetic rats were treated with 5 mg/kg/d of AS-IV for 12 weeks. Albuminuria level, relative TUG1 and TRAF5 levels, and TRAF5 and cleaved-caspase-3 protein levels were examined by ELISA, quantitative reverse transcription (qRT)-PCR, and Western blot analyses, respectively. The interaction between TUG1 and TRAF5 was confirmed by RNA pull-down and RNA precipitation. TUNEL assay was used to detect podocyte apoptosis.

Results

Compared with control rats, DN rats had higher albuminuria and TRAF5 levels and lower TUG1 level. AS-IV treatment attenuated albuminuria and TRAF5 levels and improved TUG1 level in DN rats. TUG1 was downregulated and TRAF5 was upregulated in high-glucose-treated MPC5 cells, and AS-IV ameliorated the TUG1 level. In addition, TUG1 interacted with TRAF5, and TUG1 overexpression promoted degradation of TRAF5 protein. Besides, AS-IV modulated TRAF5 expression through regulating TUG1. AS-IV decreased podocyte apoptosis via the TUG1/TRAF5 pathway. Finally, in vivo experiment proved that si-TUG1 abrogated the protective effect of AS-IV on DN.

Conclusion

AS-IV attenuated podocyte apoptosis and protected diabetic rats from DN via the lncRNA-TUG1/TRAF5 pathway.

SUBMITTER: Lei X

PROVIDER: S-EPMC6132489 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats.

Lei Xiao X Zhang Limei L Li Zonglin Z Ren Jigang J

Drug design, development and therapy 20180906

<h4>Objective</h4>This study aims to figure out the mechanism of astragaloside IV (AS-IV) in the protection of podocyte apoptosis in diabetic nephropathy (DN) rats.<h4>Materials and methods</h4>Streptozotocin (STZ) was used to induce diabetes in rats, and the diabetic rats were treated with 5 mg/kg/d of AS-IV for 12 weeks. Albuminuria level, relative TUG1 and TRAF5 levels, and TRAF5 and cleaved-caspase-3 protein levels were examined by ELISA, quantitative reverse transcription (qRT)-PCR, and Wes ...[more]

PMID: 30233141

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Project description:BackgroundDiabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats.MethodsMale Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n = 8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot.ResultsIn comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats.ConclusionAS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

Dataset Information

Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats.

Objective

Materials and methods

Results

Conclusion

Publications

Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte apoptosis of diabetic nephropathy rats.

Similar Datasets

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