Limits...
Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy

View Article: PubMed Central - PubMed

ABSTRACT

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

No MeSH data available.


Related in: MedlinePlus

IL-20 was upregulated in the serum of patients with DM. (a) The serum levels of IL-20 were analyzed in 46 healthy volunteers and 78 patients with DM. The mean levels of IL-20 were 59.70 pg ml−1 in healthy volunteers, and 309.80 pg ml−1 in DM patients. The lines inside the boxes represent the mean IL-20 values. **P<0.01 compared with healthy controls. The data are representative of three independent experiments. (b) To analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to the GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively. The lines inside the boxes represent the mean IL-20 values. *P<0.05, **P<0.01 compared with the healthy controls. The data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382560&req=5

fig6: IL-20 was upregulated in the serum of patients with DM. (a) The serum levels of IL-20 were analyzed in 46 healthy volunteers and 78 patients with DM. The mean levels of IL-20 were 59.70 pg ml−1 in healthy volunteers, and 309.80 pg ml−1 in DM patients. The lines inside the boxes represent the mean IL-20 values. **P<0.01 compared with healthy controls. The data are representative of three independent experiments. (b) To analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to the GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively. The lines inside the boxes represent the mean IL-20 values. *P<0.05, **P<0.01 compared with the healthy controls. The data are representative of three independent experiments.

Mentions: To further examine whether IL-20 was associated with diabetes mellitus (DM) and involved in the pathogenesis of DM, we analyzed the IL-20 serum levels in patients with DM and compared them with those of healthy controls. Forty-six healthy controls and 78 patients with DM were included in the analysis. The serum IL-20 concentration in DM patients was significantly higher than that in healthy controls (P=0.0027). The median and mean values of IL-20 were 13.42 and 59.70 pg ml−1 in healthy controls, and 76.11 and 309.80 pg ml−1 in patients with diabetes mellitus, respectively (Figure 6a). A decreasing glomerular filtration rate (GFR) is a valuable indicator of the progression of diabetic nephropathy. To further analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to their GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The serum IL-20 level was significantly higher in DM-group 2 and DM-group 3 than in healthy controls (Figure 6b). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively.


Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy
IL-20 was upregulated in the serum of patients with DM. (a) The serum levels of IL-20 were analyzed in 46 healthy volunteers and 78 patients with DM. The mean levels of IL-20 were 59.70 pg ml−1 in healthy volunteers, and 309.80 pg ml−1 in DM patients. The lines inside the boxes represent the mean IL-20 values. **P<0.01 compared with healthy controls. The data are representative of three independent experiments. (b) To analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to the GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively. The lines inside the boxes represent the mean IL-20 values. *P<0.05, **P<0.01 compared with the healthy controls. The data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382560&req=5

fig6: IL-20 was upregulated in the serum of patients with DM. (a) The serum levels of IL-20 were analyzed in 46 healthy volunteers and 78 patients with DM. The mean levels of IL-20 were 59.70 pg ml−1 in healthy volunteers, and 309.80 pg ml−1 in DM patients. The lines inside the boxes represent the mean IL-20 values. **P<0.01 compared with healthy controls. The data are representative of three independent experiments. (b) To analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to the GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively. The lines inside the boxes represent the mean IL-20 values. *P<0.05, **P<0.01 compared with the healthy controls. The data are representative of three independent experiments.
Mentions: To further examine whether IL-20 was associated with diabetes mellitus (DM) and involved in the pathogenesis of DM, we analyzed the IL-20 serum levels in patients with DM and compared them with those of healthy controls. Forty-six healthy controls and 78 patients with DM were included in the analysis. The serum IL-20 concentration in DM patients was significantly higher than that in healthy controls (P=0.0027). The median and mean values of IL-20 were 13.42 and 59.70 pg ml−1 in healthy controls, and 76.11 and 309.80 pg ml−1 in patients with diabetes mellitus, respectively (Figure 6a). A decreasing glomerular filtration rate (GFR) is a valuable indicator of the progression of diabetic nephropathy. To further analyze the association between IL-20 and DM patients with kidney dysfunction, 78 patients with DM were divided into four groups according to their GFR (DM-group 1, GFR>100, n=27; DM-group 2, GFR 90-100, n=6; DM-group 3, GFR 60-89, n=30; DM-group 4, GFR<60, n=15). The serum IL-20 level was significantly higher in DM-group 2 and DM-group 3 than in healthy controls (Figure 6b). The mean levels of IL-20 were 59.70, 137.51, 692.15, 392.43 and 301.70 pg ml−1 in healthy volunteers, DM-group 1, DM-group 2, DM-group 3 and DM-group 4, respectively.

View Article: PubMed Central - PubMed

ABSTRACT

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-&beta;1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-&beta;1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

No MeSH data available.


Related in: MedlinePlus