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TWEAK/Fn14 system and crescent formation in IgA nephropathy.

Sasaki Y, Shimizu Y, Suzuki Y, Horikoshi S, Tomino Y - BMC Nephrol (2015)

Bottom Line: The levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA.In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively).In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. yhsasaki@juntendo.ac.jp.

ABSTRACT

Background: The TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells. The present study examined whether the level of TWEAK is associated with histologic findings in patients with IgA nephropathy (IgAN).

Methods: The levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA. Histological findings of renal biopsy specimens of patients with IgAN were evaluated according to the Oxford classification and histological classification for IgAN in Japan. We investigated the expression of TWEAK/Fn14 in renal tissues of those patients and assessed the effect of TWEAK in glomerular mesangial cells and podocytes.

Results: The levels of uTWEAK in the patients with IgAN and other renal diseases were significantly higher than in the healthy controls (P < 0.001). In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively). In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly. We showed not only increased expression of both TWEAK and Fn14 in IgAN patients with glomerular crescents but also TWEAK-induced cell motility in podocytes.

Conclusions: The relationship between the levels of uTWEAK and clinicopathological findings observed in this study suggests that TWEAK/Fn14 system affects crescent formation and proteinuria in patients with IgAN.

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TWEAK actions on renal cellsin vitro. (A) TWEAK modulates mesangial cells proliferation. The proliferation of MMC is significantly increased following stimulation with TWEAK (10–1000 ng/ml) for a 24-hour incubation. Data are expressed as mean ± SD of five independent experiments. **P < 0.001 vs. control; *P < 0.05 vs. control. (B) MCP-1 secretion in response to TWEAK stimulation is dose and time dependent. MCP-1 protein levels in TWEAK stimulated MMC supernatants are shown. Data are expressed as mean ± SD of three independent experiments. *P < 0.05, TWEAK at 10, 100 ng/ml vs. control. (C) TWEAK stimulates podocyte motility as evaluated by wound healing assay. After the scraping of the podocyte cell layer, cells have started to migrate into the wound track. The wound closures were significantly enhanced in the presence of TWEAK (100, 1000 ng/ml) at 24 hours. Compared with the control, TWEAK enhanced directed cell migration in differentiated podocytes. Data are expressed as mean ± SD of five independent experiments. *P < 0.05, TWEAK at 100, 1000 ng/ml vs. control 24 hours. Scale bar = 200 μm.
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Fig4: TWEAK actions on renal cellsin vitro. (A) TWEAK modulates mesangial cells proliferation. The proliferation of MMC is significantly increased following stimulation with TWEAK (10–1000 ng/ml) for a 24-hour incubation. Data are expressed as mean ± SD of five independent experiments. **P < 0.001 vs. control; *P < 0.05 vs. control. (B) MCP-1 secretion in response to TWEAK stimulation is dose and time dependent. MCP-1 protein levels in TWEAK stimulated MMC supernatants are shown. Data are expressed as mean ± SD of three independent experiments. *P < 0.05, TWEAK at 10, 100 ng/ml vs. control. (C) TWEAK stimulates podocyte motility as evaluated by wound healing assay. After the scraping of the podocyte cell layer, cells have started to migrate into the wound track. The wound closures were significantly enhanced in the presence of TWEAK (100, 1000 ng/ml) at 24 hours. Compared with the control, TWEAK enhanced directed cell migration in differentiated podocytes. Data are expressed as mean ± SD of five independent experiments. *P < 0.05, TWEAK at 100, 1000 ng/ml vs. control 24 hours. Scale bar = 200 μm.

Mentions: To confirm whether TWEAK may affect the proliferation or apoptosis of kidney cells, we performed a cell proliferation assay. The proliferation of MMC was significantly increased under the stimulation of TWEAK (10–1000 ng/ml), with the highest effect at 1000 ng/ml (Figure 4A). We examined TWEAK-induced MCP-1 expression in MMC. Protein expression was increased in both the dose of TWEAK and time-dependent manners (Figure 4B).Figure 4


TWEAK/Fn14 system and crescent formation in IgA nephropathy.

Sasaki Y, Shimizu Y, Suzuki Y, Horikoshi S, Tomino Y - BMC Nephrol (2015)

TWEAK actions on renal cellsin vitro. (A) TWEAK modulates mesangial cells proliferation. The proliferation of MMC is significantly increased following stimulation with TWEAK (10–1000 ng/ml) for a 24-hour incubation. Data are expressed as mean ± SD of five independent experiments. **P < 0.001 vs. control; *P < 0.05 vs. control. (B) MCP-1 secretion in response to TWEAK stimulation is dose and time dependent. MCP-1 protein levels in TWEAK stimulated MMC supernatants are shown. Data are expressed as mean ± SD of three independent experiments. *P < 0.05, TWEAK at 10, 100 ng/ml vs. control. (C) TWEAK stimulates podocyte motility as evaluated by wound healing assay. After the scraping of the podocyte cell layer, cells have started to migrate into the wound track. The wound closures were significantly enhanced in the presence of TWEAK (100, 1000 ng/ml) at 24 hours. Compared with the control, TWEAK enhanced directed cell migration in differentiated podocytes. Data are expressed as mean ± SD of five independent experiments. *P < 0.05, TWEAK at 100, 1000 ng/ml vs. control 24 hours. Scale bar = 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4363378&req=5

Fig4: TWEAK actions on renal cellsin vitro. (A) TWEAK modulates mesangial cells proliferation. The proliferation of MMC is significantly increased following stimulation with TWEAK (10–1000 ng/ml) for a 24-hour incubation. Data are expressed as mean ± SD of five independent experiments. **P < 0.001 vs. control; *P < 0.05 vs. control. (B) MCP-1 secretion in response to TWEAK stimulation is dose and time dependent. MCP-1 protein levels in TWEAK stimulated MMC supernatants are shown. Data are expressed as mean ± SD of three independent experiments. *P < 0.05, TWEAK at 10, 100 ng/ml vs. control. (C) TWEAK stimulates podocyte motility as evaluated by wound healing assay. After the scraping of the podocyte cell layer, cells have started to migrate into the wound track. The wound closures were significantly enhanced in the presence of TWEAK (100, 1000 ng/ml) at 24 hours. Compared with the control, TWEAK enhanced directed cell migration in differentiated podocytes. Data are expressed as mean ± SD of five independent experiments. *P < 0.05, TWEAK at 100, 1000 ng/ml vs. control 24 hours. Scale bar = 200 μm.
Mentions: To confirm whether TWEAK may affect the proliferation or apoptosis of kidney cells, we performed a cell proliferation assay. The proliferation of MMC was significantly increased under the stimulation of TWEAK (10–1000 ng/ml), with the highest effect at 1000 ng/ml (Figure 4A). We examined TWEAK-induced MCP-1 expression in MMC. Protein expression was increased in both the dose of TWEAK and time-dependent manners (Figure 4B).Figure 4

Bottom Line: The levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA.In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively).In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. yhsasaki@juntendo.ac.jp.

ABSTRACT

Background: The TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells. The present study examined whether the level of TWEAK is associated with histologic findings in patients with IgA nephropathy (IgAN).

Methods: The levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA. Histological findings of renal biopsy specimens of patients with IgAN were evaluated according to the Oxford classification and histological classification for IgAN in Japan. We investigated the expression of TWEAK/Fn14 in renal tissues of those patients and assessed the effect of TWEAK in glomerular mesangial cells and podocytes.

Results: The levels of uTWEAK in the patients with IgAN and other renal diseases were significantly higher than in the healthy controls (P < 0.001). In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively). In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly. We showed not only increased expression of both TWEAK and Fn14 in IgAN patients with glomerular crescents but also TWEAK-induced cell motility in podocytes.

Conclusions: The relationship between the levels of uTWEAK and clinicopathological findings observed in this study suggests that TWEAK/Fn14 system affects crescent formation and proteinuria in patients with IgAN.

Show MeSH
Related in: MedlinePlus