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Podocin is translocated to cytoplasm in puromycin aminonucleoside nephrosis rats and in poor-prognosis patients with IgA nephropathy.

Fukuda H, Hidaka T, Takagi-Akiba M, Ichimura K, Oliva Trejo JA, Sasaki Y, Wang J, Sakai T, Asanuma K, Tomino Y - Cell Tissue Res. (2015)

Bottom Line: Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients.This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm.Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

ABSTRACT
Podocytes serve as the final barrier to urinary protein loss through a highly specialized structure called a slit membrane and maintain foot process and glomerular basement membranes. Podocyte injury results in progressive glomerular damage and accelerates sclerotic changes, although the exact mechanism of podocyte injury is still obscure. We focus on the staining gap (podocin gap) defined as the staining difference between podocin and synaptopodin, which are normally located in the foot process. In puromycin aminonucleoside nephrosis rats, the podocin gap is significantly increased (p < 0.05) and podocin is translocated to the cytoplasm on days 7 and 14 but not on day 28. Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients. This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm. Next, we find more evidence of podocin trafficking in podocytes where podocin merges with Rab5 in puromycin aminonucleoside nephrosis rats at day 14. In immunoelectron microscopy, the podocin positive area was significantly translocated from the foot process areas to the cytoplasm (p< 0.05) on days 7 and 14 in puromycin aminonucleoside nephrosis rats. Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy. In this paper, we demonstrate that the translocation of podocin by endocytosis could be a key traffic event of critical podocyte injury and that the podocin gap could indicate the prognosis of IgA nephropathy.

No MeSH data available.


Related in: MedlinePlus

a–e Double fluorescence of podocin (green), synaptopodin (synpo) (red) and merged (yellow) in PAN rats. On day 4, the expression of podocin was decreased and the snypo area seemed larger than that of podocin but on days 7 and 14, the pattern of podocin staining had changed from a linear to cytoplasmic pattern. On day 28, the areas of both stainings were similar to control conditions (day 0). Scale bars (a–e) 50 μm. f Changes in the discrepancy staining area with podocin and synpo for each time course. We measured the podocin gap, the difference in the fluorescence staining area between podocin and synpo for each time point specimen for over 50 glomeruli using specific computer software (the mathematical formula is above this legend). KS400 software; see “Materials and methods”). On days 7 and 14, the gap was significantly increased (n ≥ 50) (p < 0.05) (mean ± SE)
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Fig2: a–e Double fluorescence of podocin (green), synaptopodin (synpo) (red) and merged (yellow) in PAN rats. On day 4, the expression of podocin was decreased and the snypo area seemed larger than that of podocin but on days 7 and 14, the pattern of podocin staining had changed from a linear to cytoplasmic pattern. On day 28, the areas of both stainings were similar to control conditions (day 0). Scale bars (a–e) 50 μm. f Changes in the discrepancy staining area with podocin and synpo for each time course. We measured the podocin gap, the difference in the fluorescence staining area between podocin and synpo for each time point specimen for over 50 glomeruli using specific computer software (the mathematical formula is above this legend). KS400 software; see “Materials and methods”). On days 7 and 14, the gap was significantly increased (n ≥ 50) (p < 0.05) (mean ± SE)

Mentions: Although on days 4 and 7 the expression of podocin and synpo were decreased, they were recovered on days 14 and 28 (Fig. 2a–e). The expression of podocin seemed to follow a linear pattern (similar to the glomerular basement membrane; GBM type) on days 4 and 7 and a podocyte cell body pattern on days 14 and 28. On the other hand, the linear staining of synpo did not change during the period from day 4 to day 28. On day 0, the staining patterns of podocin and synpo were almost matched (Fig. 2a). On days 7–14, the area of podocin seemed to be translocated to the cell body area from the foot process area; however, synpo stayed in the foot process area (Fig. 2c, d).Fig. 2


Podocin is translocated to cytoplasm in puromycin aminonucleoside nephrosis rats and in poor-prognosis patients with IgA nephropathy.

Fukuda H, Hidaka T, Takagi-Akiba M, Ichimura K, Oliva Trejo JA, Sasaki Y, Wang J, Sakai T, Asanuma K, Tomino Y - Cell Tissue Res. (2015)

a–e Double fluorescence of podocin (green), synaptopodin (synpo) (red) and merged (yellow) in PAN rats. On day 4, the expression of podocin was decreased and the snypo area seemed larger than that of podocin but on days 7 and 14, the pattern of podocin staining had changed from a linear to cytoplasmic pattern. On day 28, the areas of both stainings were similar to control conditions (day 0). Scale bars (a–e) 50 μm. f Changes in the discrepancy staining area with podocin and synpo for each time course. We measured the podocin gap, the difference in the fluorescence staining area between podocin and synpo for each time point specimen for over 50 glomeruli using specific computer software (the mathematical formula is above this legend). KS400 software; see “Materials and methods”). On days 7 and 14, the gap was significantly increased (n ≥ 50) (p < 0.05) (mean ± SE)
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Related In: Results  -  Collection

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Fig2: a–e Double fluorescence of podocin (green), synaptopodin (synpo) (red) and merged (yellow) in PAN rats. On day 4, the expression of podocin was decreased and the snypo area seemed larger than that of podocin but on days 7 and 14, the pattern of podocin staining had changed from a linear to cytoplasmic pattern. On day 28, the areas of both stainings were similar to control conditions (day 0). Scale bars (a–e) 50 μm. f Changes in the discrepancy staining area with podocin and synpo for each time course. We measured the podocin gap, the difference in the fluorescence staining area between podocin and synpo for each time point specimen for over 50 glomeruli using specific computer software (the mathematical formula is above this legend). KS400 software; see “Materials and methods”). On days 7 and 14, the gap was significantly increased (n ≥ 50) (p < 0.05) (mean ± SE)
Mentions: Although on days 4 and 7 the expression of podocin and synpo were decreased, they were recovered on days 14 and 28 (Fig. 2a–e). The expression of podocin seemed to follow a linear pattern (similar to the glomerular basement membrane; GBM type) on days 4 and 7 and a podocyte cell body pattern on days 14 and 28. On the other hand, the linear staining of synpo did not change during the period from day 4 to day 28. On day 0, the staining patterns of podocin and synpo were almost matched (Fig. 2a). On days 7–14, the area of podocin seemed to be translocated to the cell body area from the foot process area; however, synpo stayed in the foot process area (Fig. 2c, d).Fig. 2

Bottom Line: Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients.This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm.Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

ABSTRACT
Podocytes serve as the final barrier to urinary protein loss through a highly specialized structure called a slit membrane and maintain foot process and glomerular basement membranes. Podocyte injury results in progressive glomerular damage and accelerates sclerotic changes, although the exact mechanism of podocyte injury is still obscure. We focus on the staining gap (podocin gap) defined as the staining difference between podocin and synaptopodin, which are normally located in the foot process. In puromycin aminonucleoside nephrosis rats, the podocin gap is significantly increased (p < 0.05) and podocin is translocated to the cytoplasm on days 7 and 14 but not on day 28. Surprisingly, the gap is also significantly increased (p < 0.05) in human kidney biopsy specimens of poor-prognosis IgA nephropathy patients. This suggests that the podocin gap could be a useful marker for classifying the prognosis of IgA nephropathy and indicating the translocation of podocin to the cytoplasm. Next, we find more evidence of podocin trafficking in podocytes where podocin merges with Rab5 in puromycin aminonucleoside nephrosis rats at day 14. In immunoelectron microscopy, the podocin positive area was significantly translocated from the foot process areas to the cytoplasm (p< 0.05) on days 7 and 14 in puromycin aminonucleoside nephrosis rats. Interestingly, podocin is also translocated to the cytoplasm in poor-prognosis human IgA nephropathy. In this paper, we demonstrate that the translocation of podocin by endocytosis could be a key traffic event of critical podocyte injury and that the podocin gap could indicate the prognosis of IgA nephropathy.

No MeSH data available.


Related in: MedlinePlus