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Expression of hepatocyte growth factor is induced by the interaction between human mesangial cells and monocytes
Takayuki Koyama1, Kazuhiko Hora, Shinji Ako
1Department of Internal Medicine II, Shinshu University School of Medicine, Matsumoto, Japan.
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.
Insights
Direct cell-to-cell contact between mesangial cells (MC) and monocytes significantly increases hepatocyte growth factor (HGF) production, crucial for glomerulonephritis pathogenesis. This interaction, alongside humoral factors, drives local HGF release in kidney disease.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Mesangial cells (MC) produce cytokines in pathological states, influencing disease progression.
- Monocyte-MC interactions may regulate cytokines like hepatocyte growth factor (HGF), vital for kidney health and glomerulonephritis.
- Limited knowledge exists on HGF production by MC and monocytes in glomerulonephritis.
Purpose of the Study:
- Investigate HGF expression in pathological conditions.
- Determine the role of cell-to-cell interactions and humoral factors in HGF production by MC and monocytes.
Main Methods:
- Co-cultured human MC (hMC) with a human monocytoid cell line (THP-1).
- Assessed HGF mRNA expression and protein production.
- Utilized immunohistochemical staining and noncontact co-cultures to differentiate cell-contact and humoral factor contributions.
Main Results:
- Co-culture systems showed a time-dependent, fourfold increase in HGF concentration compared to hMC alone.
- Increased HGF mRNA expression was observed.
- Both hMC and THP-1 cells stained positive for HGF; noncontact co-cultures showed moderate HGF increase, indicating a role for humoral factors.
Conclusions:
- Direct cell-to-cell interaction between hMC and monocytes significantly induces HGF production in both cell types.
- This cell-to-cell interaction-mediated local HGF production is critical in glomerulonephritis pathogenesis.
- Humoral factors may also contribute to HGF production, though direct contact is more impactful.