Abstract
The increased prevalence of aging-related chronic kidney disease (CKD) among humans is a problem worldwide. Aged cotton rats (Sigmodon hispidus) are considered novel model animals for studying CKD, especially as the females develop severe tubulointerstitial lesions with anemia. To investigate the renal pathologic features in aged male cotton rats and their characteristic glomerular injuries, the animals were divided into young, adult, old-aged, and advanced-aged groups (1–4, 5–8, 9–12, and 13–17 months, respectively) and pathologically analyzed. Anemia and renal dysfunction, as indicated by hematologic and serologic parameters, were significantly milder in the advanced-aged males than in the old-aged females. The males had increased urinary albumin-to-creatinine ratios from the old-age period, with the advanced-aged males having significantly higher levels than those in the old-aged females and young males. The old-aged females did not show clear glomerular injuries, whereas the advanced-aged males showed membranous lesions characterized by irregular and thickened glomerular basement membranes (GBMs). Characteristically, several large-sized projections from the GBM toward the podocytes were observed by microscopy, and podocytes covering these projections effaced their foot processes. The advanced-aged males showed aging-related IgG immune-complex depositions in the paramesangial regions and along the GBM. Furthermore, the positive reaction for podocin (a podocyte molecule) was granulated along the GBM. Thus, we clarified the albuminuria associated with altered glomerular structures in advanced-aged cotton rats, and that these phenotypes were closely associated with aging. These data help to clarify the aging-related pathogenesis of glomerular injury.
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Abbreviations
- CKD:
-
Chronic kidney disease
- GBM:
-
Glomerular basement membrane
- BUN:
-
Blood urea nitrogen
- sCr:
-
Serum creatinine
- WBC:
-
White blood cell
- RBC:
-
Red blood cell
- Hgb:
-
Hemoglobin
- HCT:
-
Hematocrit
- SDS-PAGE:
-
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- uCr:
-
Urinary creatinine
- PAS:
-
Periodic acid Schiff
- PAM:
-
Periodic acid methenamine silver
- PBS:
-
Phosphate-buffered saline
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This work was supported by JSPS KAKENHI (Grant No.: JP18K0703708).
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O.I., T.N., T.I., T.H., Y.H.A.E., and Y.K. conceived and designed the experiments. O.I., T.N., T.I., Y.O., M.H., M.A.M., and R.M.I. performed the experiments. O.I., T.N., and Y.S. analyzed the data. O.I. and Y.K. wrote the paper.
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The animal experimentation was performed according to the guidelines of the Hokkaido Institute of Public Health, Sapporo, Japan (Approval No.: K27-03).
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418_2019_1824_MOESM1_ESM.tif
Supplemental Fig. S1 Castration analysis of male cotton rats. a. Time course of castration (Cast) and sampling. b. Urinary protein-to-creatinine ratio (uPCR) and urinary albumin-to-creatinine ratio (uACR). N.S.: not significant (TIFF 12706 kb)
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Ichii, O., Nakamura, T., Irie, T. et al. Age-related glomerular lesions with albuminuria in male cotton rats. Histochem Cell Biol 153, 27–36 (2020). https://doi.org/10.1007/s00418-019-01824-1
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DOI: https://doi.org/10.1007/s00418-019-01824-1