Expression of hepatocyte growth factor is induced by the interaction between human mesangial cells and monocytes

Abstract

Background: In pathological states various cytokines are produced by mesangial cells (MC) and contribute to disease progression. It is likely that interactions between monocytes and MC partially regulate these cytokines, including hepatocyte growth factor (HGF). Because HGF might have a potent therapeutic effect on the kidney, it is believed to play a critical role in the pathogenesis and development of glomerulonephritis. However, there is little knowledge about HGF production by MC or infiltrated monocytes in glomerulonephritis.

Methods: To investigate HGF expression in pathological states, we cultured human MC (hMC) with a human monocytoid cell line and assessed HGF mRNA expression and protein production. Next, we performed immunohistochemical staining to explore which types of cell in the co-culture system expressed HGF. Because several humoral factors that can induce HGF production have been reported, we also performed noncontact co-culture to explore the contribution of humoral factors.

Results: The HGF concentration of the co-culture system showed a time-dependent increase, and was fourfold greater than that of hMC alone. Expression of HGF mRNA was also increased. Both THP-1 cells and hMC in the co-culture demonstrated staining of HGF. The HGF concentration in the noncontact co-cultures was smaller than in the ordinary ones, but was greater than hMC alone.

Conclusion: Direct cell-to-cell interaction between hMC and monocytes induced HGF production of both types of cells, indicating that local HGF production induced by cell-to-cell interaction plays an important role in the pathogenesis of glomerulonephritis. While direct cell-to-cell contact was important for HGF production, it is considered that some humoral factors might contribute.