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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), synpo (red) and merged (yellow) in IgA Nephropathy. In IgAN-good, −r-good and -r-poor specimens, the staining areas of podocin and synpo were almost the same but the IgAN-poor podocin area (not merged with synpo, green) was larger than that of the other groups and the staining pattern had changed from a linear type to cell body type. Scale bars (a–e) 50 μm. f The changes in the discrepancy staining area with podocin and synpo in each prognosis categories of IgAN. We measured the podocin gap (see Fig. 2f). In IgAN-r-good specimens, the gap was decreased as compared with that of the control but interestingly, in the IgAN-poor group, the gap was significantly increased (p < 0.05) compared with that of IgAN-r-good control specimens, i.e., minor glomerular abnormality (n ≥ 4) (mean ± SE)
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Fig4: a–e Double fluorescence of podocin (green), synpo (red) and merged (yellow) in IgA Nephropathy. In IgAN-good, −r-good and -r-poor specimens, the staining areas of podocin and synpo were almost the same but the IgAN-poor podocin area (not merged with synpo, green) was larger than that of the other groups and the staining pattern had changed from a linear type to cell body type. Scale bars (a–e) 50 μm. f The changes in the discrepancy staining area with podocin and synpo in each prognosis categories of IgAN. We measured the podocin gap (see Fig. 2f). In IgAN-r-good specimens, the gap was decreased as compared with that of the control but interestingly, in the IgAN-poor group, the gap was significantly increased (p < 0.05) compared with that of IgAN-r-good control specimens, i.e., minor glomerular abnormality (n ≥ 4) (mean ± SE)

Mentions: Each of the four IgAN groups consisted in four samples that were stained with podocin and synpo (Fig. 4a–e). In the IgAN-good group, the podocin and synpo stained areas were consistently similar to day 0 in PAN rats (Fig. 4b, IgAN-good). In the IgAN-r-good group, the level of expression was decreased but both of them were merged completely (Fig. 4c, IgAN-r-good). In the IgAN-r-poor group, there was no evident change from the IgAN-good group (Fig. 4d, IgAN-r-poor). Surprisingly, in the IgAN-poor group, podocin was stained in the cell bodies of podocytes and there was a clear difference in the staining pattern between podocin and synpo. This result suggests the translocation of podocin to the cytoplasm. We also measured the podocin gap in each human biopsy sample from IgAN (Fig. 4f) using the previously mentioned software. The podocin gap was not altered in the IgAN-r-good and IgAN-r-poor groups when compared to the control group. However, in the IgAN-poor group it was significantly increased (p < 0.05) when compared to the area of the IgAN-r-good group, indicating that podocin translocated to the cell bodies of podocytes.Fig. 4


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), synpo (red) and merged (yellow) in IgA Nephropathy. In IgAN-good, −r-good and -r-poor specimens, the staining areas of podocin and synpo were almost the same but the IgAN-poor podocin area (not merged with synpo, green) was larger than that of the other groups and the staining pattern had changed from a linear type to cell body type. Scale bars (a–e) 50 μm. f The changes in the discrepancy staining area with podocin and synpo in each prognosis categories of IgAN. We measured the podocin gap (see Fig. 2f). In IgAN-r-good specimens, the gap was decreased as compared with that of the control but interestingly, in the IgAN-poor group, the gap was significantly increased (p < 0.05) compared with that of IgAN-r-good control specimens, i.e., minor glomerular abnormality (n ≥ 4) (mean ± SE)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: a–e Double fluorescence of podocin (green), synpo (red) and merged (yellow) in IgA Nephropathy. In IgAN-good, −r-good and -r-poor specimens, the staining areas of podocin and synpo were almost the same but the IgAN-poor podocin area (not merged with synpo, green) was larger than that of the other groups and the staining pattern had changed from a linear type to cell body type. Scale bars (a–e) 50 μm. f The changes in the discrepancy staining area with podocin and synpo in each prognosis categories of IgAN. We measured the podocin gap (see Fig. 2f). In IgAN-r-good specimens, the gap was decreased as compared with that of the control but interestingly, in the IgAN-poor group, the gap was significantly increased (p < 0.05) compared with that of IgAN-r-good control specimens, i.e., minor glomerular abnormality (n ≥ 4) (mean ± SE)
Mentions: Each of the four IgAN groups consisted in four samples that were stained with podocin and synpo (Fig. 4a–e). In the IgAN-good group, the podocin and synpo stained areas were consistently similar to day 0 in PAN rats (Fig. 4b, IgAN-good). In the IgAN-r-good group, the level of expression was decreased but both of them were merged completely (Fig. 4c, IgAN-r-good). In the IgAN-r-poor group, there was no evident change from the IgAN-good group (Fig. 4d, IgAN-r-poor). Surprisingly, in the IgAN-poor group, podocin was stained in the cell bodies of podocytes and there was a clear difference in the staining pattern between podocin and synpo. This result suggests the translocation of podocin to the cytoplasm. We also measured the podocin gap in each human biopsy sample from IgAN (Fig. 4f) using the previously mentioned software. The podocin gap was not altered in the IgAN-r-good and IgAN-r-poor groups when compared to the control group. However, in the IgAN-poor group it was significantly increased (p < 0.05) when compared to the area of the IgAN-r-good group, indicating that podocin translocated to the cell bodies of podocytes.Fig. 4

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