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.

• Authors: Xiao Lei, Limei Zhang, Zonglin Li, Jigang Ren
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 12 Pg. 2785-2793 ( 2018) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 30233141 (Publication Type: Journal Article)

Chemical References

• RNA, Long Noncoding
• Saponins
• TNF Receptor-Associated Factor 5
• TUG1 long noncoding RNA, rat
• Triterpenes
• astragaloside A
• Streptozocin

Topics

• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Diabetic Nephropathies (chemically induced, drug therapy, pathology)
• Male
• Mice
• Podocytes (drug effects, metabolism)
• RNA, Long Noncoding (antagonists & inhibitors, biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Saponins (administration & dosage, pharmacology)
• Signal Transduction (drug effects, genetics)
• Streptozocin
• Structure-Activity Relationship
• TNF Receptor-Associated Factor 5 (biosynthesis, genetics)
• Triterpenes (administration & dosage, pharmacology)