Effects of mycophenolate mofetil on the expression of monocyte chemoattractant protein-1 and fibronectin in high glucose cultured human mesangial cells

Abstract

ABSTRACT. The effects of high glucose on the expression of monocyte chemoattractant protein-1 (MCP-1) and the main component of the extracellular matrix, fibronectin (FN), were explored in human mesangial cells (HMCs), along with the intervention effects of mycophenolate mofetil (MMF) on these indicators. Cultured HMCs were divided into five groups: 1) normal control group (5 mM glucose); 2) high glucose group (30 mM glucose); 3) mannitol osmotic pressure control group (5 mM glucose + 25 mM mannitol); 4) high glucose + MMF-10 group (30 mM glucose + 10 μg/mL MMF); 5) high glucose + MMF-100 group (30 mM glucose + 100 μg/mL MMF). At 24, 48, and 72 h, reverse transcription-polymerase chain reaction and enzymelinked immunosorbent assay methods were used to detect the effects of MMF on MCP-1 mRNA and protein and FN expression in HMCs under MCP-1 and fibronectin high glucose conditions. MCP-1 mRNA and protein expressions and FN secretion significantly increased in HMCs of the high glucose group compared with the normal control group (P < 0.01), with the highest expression observed at 48 h. MMF could reduce the MCP-1 mRNA and protein and FN expression levels (P < 0.01), and the inhibition occurred in a dose-and time-dependent manner (P < 0.05). In conclusion, MMF could inhibit MCP-1 expression and the secretion of FN, indicating that it may delay the progression of glomerulosclerosis and interstitial fibrosis in diabetic nephropathy to ultimately achieve protective effects on the kidney.

Metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through the SIRT1‐FOXO1‐autophagy axis

“…19 Mounting evidence demonstrates that the expression of fibronectin and collagen IV is upregulated in RMCs in response to high glucose conditions. 20 Recently, many studies have demonstrated that inflammation has a central role in the progression of diabetic nephropathy. 21 High glucose upregulates the expression of inflammatory factors.…”

Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose

“…Next, in order to rule out the possibility that the high osmotic pressure in the high-dose glucose solution affected the NET formation, we employed mannitol with osmotic pressure similar to glucose [15]. Since the exposure to 20 m M glucose, but not to mannitol, for 2 h at 37°C induced NETs (fig.…”

Potential Renoprotective Agents through Inhibiting CTGF/CCN2 in Diabetic Nephropathy

“…MPA might downregulate the expression of TGF- β and CCN2 by reducing intracellular GTP accumulation via suppressing the activity of IMPDH, deactivating most G protein and blocking intracellular signal pathway [ 63 ]. A recent study also demonstrated that the expression of monocyte chemoattractant protein-1 (MCP-1) as well as the secretion of fibronectin (FN) was inhibited by MMF in human mesangial cells (HMCs) exposed to high glucose [ 64 ]. These results suggested that MMF played the antifibrotic effect on diabetic nephropathy through suppressing CCN2 and FN expression.…”