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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.

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An IL-20R1 deficiency reduced the severity of STZ-induced diabetic nephropathy. (a) Blood glucose measurements in IL-20R1+/+, IL-20R1+/− and IL-20R1−/− mice from day 5 to 49 after STZ treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments. (b) Survival in each group (n=8 per group) was monitored daily until the end of the experiment. The data are representative of three independent experiments. (c, d) Serum BUN levels and renal glomerular areas on day 49 were analyzed in IL-20R1+/+, IL-20R1+/−, and IL-20R1−/− mice after STZ or control buffer treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments.
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fig3: An IL-20R1 deficiency reduced the severity of STZ-induced diabetic nephropathy. (a) Blood glucose measurements in IL-20R1+/+, IL-20R1+/− and IL-20R1−/− mice from day 5 to 49 after STZ treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments. (b) Survival in each group (n=8 per group) was monitored daily until the end of the experiment. The data are representative of three independent experiments. (c, d) Serum BUN levels and renal glomerular areas on day 49 were analyzed in IL-20R1+/+, IL-20R1+/−, and IL-20R1−/− mice after STZ or control buffer treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments.

Mentions: IL-20R1 was upregulated in the kidneys of mice with STZ-induced diabetes (Figure 1c), which suggested that IL-20R1 might be important for IL-20-mediated inflammatory responses and might be involved in the pathogenesis of diabetic nephropathy. Therefore, we investigated the effect of an IL-20R1 deficiency on IL-20-mediated early diabetic nephropathy. To confirm the in vivo role of IL-20 in diabetic nephropathy, we used the STZ-induced diabetic model to investigate whether IL-20R1 receptor signaling was important for controlling disease processes. STZ-induced diabetes resulted in higher blood glucose levels, higher serum BUN levels, and an enlarged glomerulus. Blood glucose was significantly (P<0.05) lower in STZ-IL-20R1−/− mice than in STZ-IL-20R1+/+ mice (Figure 3a). The STZ-IL-20R1−/− mice had a longer survival rate than the STZ-IL-20R1+/+ mice (Figure 3b). The serum BUN levels in STZ-IL-20R1−/− mice were lower than those in STZ-IL-20R1+/+ mice (Figure 3c). Glomerular enlargement during diabetes is an indication of renal damage. Thus, we measured the average glomerular area of the cross-section. The average glomerular area was lower in STZ-IL-20R1−/− mice than in the STZ-IL-20R1+/+ controls (Figure 3d) on day 49 after STZ induction.


Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy
An IL-20R1 deficiency reduced the severity of STZ-induced diabetic nephropathy. (a) Blood glucose measurements in IL-20R1+/+, IL-20R1+/− and IL-20R1−/− mice from day 5 to 49 after STZ treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments. (b) Survival in each group (n=8 per group) was monitored daily until the end of the experiment. The data are representative of three independent experiments. (c, d) Serum BUN levels and renal glomerular areas on day 49 were analyzed in IL-20R1+/+, IL-20R1+/−, and IL-20R1−/− mice after STZ or control buffer treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments.
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fig3: An IL-20R1 deficiency reduced the severity of STZ-induced diabetic nephropathy. (a) Blood glucose measurements in IL-20R1+/+, IL-20R1+/− and IL-20R1−/− mice from day 5 to 49 after STZ treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments. (b) Survival in each group (n=8 per group) was monitored daily until the end of the experiment. The data are representative of three independent experiments. (c, d) Serum BUN levels and renal glomerular areas on day 49 were analyzed in IL-20R1+/+, IL-20R1+/−, and IL-20R1−/− mice after STZ or control buffer treatment (n=8 per group). *P<0.05 compared with IL-20R1+/+ mice. The data are expressed as the mean±s.e.m. of three independent experiments.
Mentions: IL-20R1 was upregulated in the kidneys of mice with STZ-induced diabetes (Figure 1c), which suggested that IL-20R1 might be important for IL-20-mediated inflammatory responses and might be involved in the pathogenesis of diabetic nephropathy. Therefore, we investigated the effect of an IL-20R1 deficiency on IL-20-mediated early diabetic nephropathy. To confirm the in vivo role of IL-20 in diabetic nephropathy, we used the STZ-induced diabetic model to investigate whether IL-20R1 receptor signaling was important for controlling disease processes. STZ-induced diabetes resulted in higher blood glucose levels, higher serum BUN levels, and an enlarged glomerulus. Blood glucose was significantly (P<0.05) lower in STZ-IL-20R1−/− mice than in STZ-IL-20R1+/+ mice (Figure 3a). The STZ-IL-20R1−/− mice had a longer survival rate than the STZ-IL-20R1+/+ mice (Figure 3b). The serum BUN levels in STZ-IL-20R1−/− mice were lower than those in STZ-IL-20R1+/+ mice (Figure 3c). Glomerular enlargement during diabetes is an indication of renal damage. Thus, we measured the average glomerular area of the cross-section. The average glomerular area was lower in STZ-IL-20R1−/− mice than in the STZ-IL-20R1+/+ controls (Figure 3d) on day 49 after STZ induction.

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