Abstract
Diabetic nephropathy (DN) is the common complications of diabetes mellitus, but the efficacy of available treatments for the prevention of DN is still unsatisfactory. In the present study, we aimed to explore the effect of Danggui buxue tang (DGT) on the proliferation of high glucose (HG)-induced mesangial cells and accumulation of extracellular matrix in mesangial cells. We found DGT up-regulated the expression of growth arrest specific transcript 5 (GAS5) and IκB kinase (IKK) dose-dependently in mouse mesangial cells (SV40 MES-13). We found DGT regulated the expression IKK and the activity of nuclear transcription factor-κB (NF-κB) via GAS5, and proved that long non-coding RNA (lncRNA) GAS5 was positively related with IKK. And we proved GAS5 regulated the expression of IKK and the activity of NF-κB. In addition, DGT inhibited the viability of MES-13 cells and extracellular matrix-related proteins (laminin (LN), fibronectin (FN) and collagen IV (Col IV)) via GAS5. Moreover, we proved GAS5 regulated the viability of SV40 MES-13 cells and extracellular matrix-related proteins through NF-κB pathway. DGT inhibited the proliferation of mesangial cells and accumulation of extracellular matrix via GAS5/NF-κB, therefore, DGT could be an effective treatment for the prevention of DN.
Highlights
Diabetic nephropathy (DN) is one of the most important and common complications of diabetes mellitus, which is characterized by persistent increment of urinary albumin or protein
high glucose (HG) down-regulated the expression of IκB kinase (IKK), while DGTXT up-regulated the expression of IKK dose-dependently (Figure 1B), indicating that DGTXT could increase the expression of IKK, which meant DGTXT inhibited nuclear transcription factor-κB (NF-κB) signaling pathway
To find out how Danggui buxue tang (DGT) participated in the expression of IKK and the activity of NF-κB regulated by HG, silencing growth arrest specific transcript 5 (GAS5) was used to observe the changes of IKK and NF-κB
Summary
Diabetic nephropathy (DN) is one of the most important and common complications of diabetes mellitus, which is characterized by persistent increment of urinary albumin or protein. It can result in the loss of renal function and lead to the failure of renal function [1,2]. The main pathological features of DN are renal interstitial fibrosis, nephropyelitis, renal papillary necrosis and renal arteriosclerosis. The main therapeutic strategies are tight control of blood glucose and blood pressure, low-protein diet, lipid-lowering and drug therapies [4,5]. The efficacy of available treatments for the prevention of DN is still unsatisfactory
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