Porphyromonas gingivalis-derived lipopolysaccharide promotes mesangial cell fibrosis via transforming growth factor-beta1/Smad signaling pathway in high glucose.

BACKGROUND/PURPOSE: Periodontitis has been documented to increase the risk of diabetic nephropathy. However, the specific mechanisms through which periodontitis affects renal function remain unclear. This study aimed to investigate the mechanism by which an inflammatory reaction stimulated by periodontal pathogens affects mesangial cell fibrosis under hyperglycemic conditions

MATERIALS AND METHODS

Murine mesangial cells were stimulated with 1,000 ng/mL of -derived lipopolysaccharide (LPS) in a control or high glucose (HG) medium. Activation of the extracellular signal-regulated kinase (ERK1/2) and expression of alpha-smooth muscle actin (α-SMA) and collagen type 1a2 () were analyzed for fibrosis and transformation via the transforming growth factor (TGF)-β1/Smad signaling pathway.

RESULTS

LPS stimulation significantly upregulated TGF-β1 expression and Smad3 phosphorylation in the HG group compared to the control group. Additionally, activation of ERK1/2 and expression of and α-SMA were significantly elevated in the HG group compared to the control following LPS stimulation. The TGF-β1 inhibitor significantly suppressed Smad3 phosphorylation and mRNA expression of in the HG group.

CONCLUSION

Under HG conditions, LPS may aggravate fibrosis in mesangial cells via the TGF-β1/Smad signaling pathway, leading to nephrosclerotic modifications. The presented study may support the association between periodontitis and chronic kidney disease, mediated by hyperglycemia.