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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–c Immunoelectron microscopy of podocin in PAN rats. Podocin moved from the slit diaphragm area to the cytoplasmic area as a form of vesicles at day 14 in the podocytes. Scale bars (a–c, a’–c’)50 nm. Left low-magnification images (×8000–×20,000) and right high-magnification images (×10,000–×50,000). d Podocin significantly moved to the cytoplasm of podocytes on days 7 and 14 in PAN rats. The number of gold particles (podocin) was calculated in the cytoplasmic area of podocytes. On days 7 and 14, podocin was significantly increased in the cytoplasmic area in podocytes (n ≥ 15) (p < 0.05) (mean ± SE)
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Fig3: a–c Immunoelectron microscopy of podocin in PAN rats. Podocin moved from the slit diaphragm area to the cytoplasmic area as a form of vesicles at day 14 in the podocytes. Scale bars (a–c, a’–c’)50 nm. Left low-magnification images (×8000–×20,000) and right high-magnification images (×10,000–×50,000). d Podocin significantly moved to the cytoplasm of podocytes on days 7 and 14 in PAN rats. The number of gold particles (podocin) was calculated in the cytoplasmic area of podocytes. On days 7 and 14, podocin was significantly increased in the cytoplasmic area in podocytes (n ≥ 15) (p < 0.05) (mean ± SE)

Mentions: In the immunoelectron microscopy of PAN rats, immunoreactive podocin was recognized by gold particles (Fig. 3a, b, c: low magnification ×8000–×20,000, 3a’, b’, c’: high magnification ×10,000–×50,000). On day 0, podocin was recognized at the slit diaphragm insertion sites of foot processes (Fig. 3a, day 0). On day 7, the structure of the slit diaphragm was destroyed and the podocin was translocated to the cell bodies of the podocytes (Fig. 3b, day 7). On day 14, through staining, podocin was seen in the vesicular structures in the cell bodies of podocytes (Fig. 3c, day 14). These data indicate that the podocin was translocated to the cell body, likely by endocytosis.Fig. 3


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–c Immunoelectron microscopy of podocin in PAN rats. Podocin moved from the slit diaphragm area to the cytoplasmic area as a form of vesicles at day 14 in the podocytes. Scale bars (a–c, a’–c’)50 nm. Left low-magnification images (×8000–×20,000) and right high-magnification images (×10,000–×50,000). d Podocin significantly moved to the cytoplasm of podocytes on days 7 and 14 in PAN rats. The number of gold particles (podocin) was calculated in the cytoplasmic area of podocytes. On days 7 and 14, podocin was significantly increased in the cytoplasmic area in podocytes (n ≥ 15) (p < 0.05) (mean ± SE)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig3: a–c Immunoelectron microscopy of podocin in PAN rats. Podocin moved from the slit diaphragm area to the cytoplasmic area as a form of vesicles at day 14 in the podocytes. Scale bars (a–c, a’–c’)50 nm. Left low-magnification images (×8000–×20,000) and right high-magnification images (×10,000–×50,000). d Podocin significantly moved to the cytoplasm of podocytes on days 7 and 14 in PAN rats. The number of gold particles (podocin) was calculated in the cytoplasmic area of podocytes. On days 7 and 14, podocin was significantly increased in the cytoplasmic area in podocytes (n ≥ 15) (p < 0.05) (mean ± SE)
Mentions: In the immunoelectron microscopy of PAN rats, immunoreactive podocin was recognized by gold particles (Fig. 3a, b, c: low magnification ×8000–×20,000, 3a’, b’, c’: high magnification ×10,000–×50,000). On day 0, podocin was recognized at the slit diaphragm insertion sites of foot processes (Fig. 3a, day 0). On day 7, the structure of the slit diaphragm was destroyed and the podocin was translocated to the cell bodies of the podocytes (Fig. 3b, day 7). On day 14, through staining, podocin was seen in the vesicular structures in the cell bodies of podocytes (Fig. 3c, day 14). These data indicate that the podocin was translocated to the cell body, likely by endocytosis.Fig. 3

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