Morphometric Study of Gender Differences with Regard to Age-Related Changes in the C57BL/6 Mouse Kidney

Yabuki, Akira; Tanaka, Shin; Matsumoto, Mitsuharu; Suzuki, Syusaku

doi:10.1538/expanim.55.399

Cited by 23 publications

(15 citation statements)

References 22 publications

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“…In contrast, there were very few gene expression changes between 6 and 44 weeks. In the future, it would be interesting to follow the podocyte transcriptome out to later timepoints, since marked glomerular changes are seen in very old (36 months) mice (61), and these may correspond to age-related GFR loss observed in older humans.…”

Section: Discussionmentioning

confidence: 99%

Discovery of new glomerular disease–relevant genes by translational profiling of podocytes in vivo

Grgic

Hofmeister

Bernhardy

et al. 2014

Kidney International

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Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. Expressed eGFP-tagged ribosomal protein L10a in podocytes under the control of the Collagen-1α1 promoter enabled podocyte-specific mRNA isolation in a one-step process over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed col1α1-L10a mice with the actn4−/− and actn4+/K256E models of FSGS and analyzed podocyte transcriptional profiles at 2, 6 and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression datasets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and help define novel biomarkers and therapeutic targets for human glomerular disease.

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Section: Discussionmentioning

confidence: 99%

Discovery of new glomerular disease–relevant genes by translational profiling of podocytes in vivo

Grgic

Hofmeister

Bernhardy

et al. 2014

Kidney International

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“…14 In mice, the C57BL6 strain is more resistant to renal aging than other strains, and morphologic changes of aging are milder in female mice versus males. 15,16 Female C57BL6 mice begin to have irregular, lengthened estrous cycles around 10 to 14 mo of age, and cycles usually cease at 13 to 16 mo of age. 17 Dr. Striker's group has shown glomerular hypertrophy, vascular pole sclerosis, and mesangial cell proliferation in 18-mo-old C57BL6 female mice, 18 while we used renal-sclerosis-prone 129/Sv mice.…”

Section: Discussionmentioning

confidence: 99%

Cells Derived from Young Bone Marrow Alleviate Renal Aging

Yang

Rossini²,

Ma³

et al. 2011

Journal of the American Society of Nephrology

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Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less ␤-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show ␤-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor ␤. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

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“…The number of normal glomeruli is reduced with age in male Munich Wistar rats, but not in females, whereas the glomerular volume increases in both genders, but more prominently in male rats (27). Conversely, aged female C57 mice present a markedly increased renal corpuscle diameter compared to males, although glomerular damage and interstitial fibrosis are more severe in males than in females (28). Structural changes include thickening of the glomerular basement membrane, expansion of the glomerular mesangium and EMP deposition leading to glomerular sclerosis (1).…”

Section: Morphological Changesmentioning

confidence: 90%