Danggui buxue tang suppresses high glucose-induced proliferation and extracellular matrix accumulation of mesangial cells via inhibiting lncRNA PVT1.

BACKGROUND: Danggui Buxue Tang (DBT), a traditional Chinese medicine decoction, has been proven to have satisfactory effects on treating diabetic nephropathy (DN). In this study, we explored the potential underlying mechanism of DBT in DN treatment.

METHODS: The DBT-containning serum was prepared by intragastric administration with DBT for rats. The levels of fibronectin (FN), laminin (LN) and collagen IV (COL IV) and TGF-β1 protein secreted in cell culture medium were determined by ELISA assay. The mRNA and protein expression of related molecule was measured using qRT-PCR and western blotting. MTT assay was applied to test MCs proliferation.

RESULTS: DBT has a negative effect on the high glucose (HG)-induced proliferation and extracellular matrix (ECM) accumulation of mesangial cells (MCs). Further research showed that DBT reduced the acetylation level of histone H3 at the site of PVT1 promoter to promote PVT1 downregulation, which was accompanied by a decrease in TGF-β and c-myc expression. Moreover, PVT1 overexpression significantly enhanced cell viability and promoted the expression levels of TGF-β1 and c-myc. Furthermore, PVT1 overexpression significantly reversed the inhibition of DBT on HG-induced cell viability and ECM accumulation and also lifted the effect of DBT on TGF-β1 and c-myc expression.

CONCLUSION: DBT inhibited TGF-β1 and c-myc expression through downregulating PVT1, and thus attenuated MCs excessive proliferation and ECM accumulation in DN.