Age-associated changes in renal glomeruli of mice

Yumura, Wako; Sugino, Nobuhiro; Nagasawa, Ryo; Kubo, Sachiho; Hirokawa, Katsuíku; Maruyama, Naoki

doi:10.1016/0531-5565(89)90015-6

Cited by 37 publications

(28 citation statements)

References 15 publications

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“…26,[28][29][30] It was unclear until now whether lost podocytes were at least partially regenerated and if age-related glomerulosclerosis was, thus, caused by an insufficient replacement of podocytes. 31 The aged PEC-rtTA mice showed typical changes within the glomerulus associated with kidney aging 27 (i.e., mesangial matrix expansion, thickening of the GBM with formation of spikes/humps, proteinuria, and podocyte hypertrophy). Despite these structural changes, no replacement of podocytes by PECs was detected, even in these very old mice.…”

Section: Discussionmentioning

confidence: 99%

“…This finding is consistent with our previous reports. [17][18][19]27 In the current study, we examined podocyte regeneration under physiologic conditions and in models of glomerular hypertrophy. The choice to use these models was made for several reasons.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of renal function and development of glomerulosclerosis are associated with aging in humans as well as rodents. [23][24][25][26][27] Several studies have indicated that loss of podocytes plays an important role in age-related glomerulosclerosis. 26,[28][29][30] It was unclear until now whether lost podocytes were at least partially regenerated and if age-related glomerulosclerosis was, thus, caused by an insufficient replacement of podocytes.…”

Section: Discussionmentioning

confidence: 99%

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The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Berger¹,

Schulte²,

Kuppe³

et al. 2014

Journal of the American Society of Nephrology

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Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glomerular hypertrophy was induced by progressive partial nephrectomies. Again, no significant podocyte replenishment was observed. Rather, labeled PECs exclusively invaded segments of the tuft affected by glomerulosclerosis, consistent with our previous findings. We next reassessed PEC recruitment in juvenile mice using a different reporter mouse and confirmed significant recruitment of labeled PECs onto the glomerular tuft. Moreover, some labeled cells on Bowman's capsule expressed podocyte markers, and cells on Bowman's capsule were also directly labeled in juvenile podocyte-specific Pod-rtTA transgenic mice. In 6-week-old mice, however, cells on Bowman's capsule no longer expressed podocyte-specific markers. Similarly, in human kidneys, some cells on Bowman's capsule expressed the podocyte marker synaptopodin from 2 weeks to 2 years of age but not at 7 years of age. In summary, podocyte regeneration from PECs could not be detected in aging mice or models of glomerular hypertrophy. We propose that a small fraction of committed podocytes reside on Bowman's capsule close to the vascular stalk and are recruited onto the glomerular tuft during infancy to adolescence in mice and humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Berger¹,

Schulte²,

Kuppe³

et al. 2014

Journal of the American Society of Nephrology

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“…Polyclonal rabbit anti-mouse albumin antibody (Ab) was made as described [25]. Rat anti-murine Mac-1 MoAb (M1-70.15.11.5.HL) was obtained from the American Tissue Culture Collection (ATCC).…”

Section: Polyclonal and Monoclonal Antibodiesmentioning

confidence: 99%

“…The concentration of albumin in urine was determined by single radial immunodiffusion (SRID) using specific Ab for mouse albumin [25] as described previously [28].…”

Section: Single Radial Immunodiffusionmentioning

confidence: 99%

Macrophage-colony stimulating factor (M-CSF) enhances proteinuria and recruitment of macrophages into the glomerulus in experimental murine nephritis

Utsunomiya

Omura

Yokoo

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIn this study, we examined the effects of macrophage-colony stimulating factor (M-CSF) on glomerular macrophages in lipopolysaccharide (LPS)-induced murine nephritis. Mice injected intraperitoneally with either M-CSF plus LPS, LPS alone, M-CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyte-function associated antigen-1-positive (LFA-1 ) cells in peripheral blood as well as renal pathology. From our results, LPS or M-CSF combined with LPS emphasized the degree of proteinuria, glomerular deposition of immunoglobulins and mesangial proliferation, associated with accumulation of macrophages in the glomeruli. However, in immunohistological examination of kidneys from these nephritic mice, neither intercellular adhesion molecule-1 (ICAM-1), which may play an important role in the recruitment of macrophages into glomeruli, M-CSF receptor nor the number of LFA-1 cells in peripheral blood was enhanced by M-CSF. On the other hand, M-CSF alone induced neither proteinuria nor any pathological changes and did not increase the number of glomerular Mac-1 cells above that in saline-treated controls. These results indicate that M-CSF does not directly cause glomerulonephritis but might participate in accelerating the glomerular inflammatory process by stimulating a potent chemoattractant to recruit monocytes-macrophages into the glomeruli.

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Renal ageing

Martin

Sheaff

2007

The Journal of Pathology

197

148

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The function of the kidney, as well as its morphology, changes markedly with age. The glomerular filtration rate falls progressively, independent of overt pathology. Glomerular, vascular and accompanying parenchymal changes occur and other disorders associated with ageing, such as diabetes and hypertension, have a stochastic deleterious effect on both form and function. Declining renal function with age has important implications, not only for individual homeostasis but also for the use of drug therapy and for the receipt and donation of organs for transplantation. Molecular mechanisms and cellular changes underlying some of the functional and structural changes associated with ageing are becoming clearer, as are some of the ways in which genetic background, age and disease can combine to produce functional damage.

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Age-associated changes in renal glomeruli of mice

Cited by 37 publications

References 15 publications

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

Macrophage-colony stimulating factor (M-CSF) enhances proteinuria and recruitment of macrophages into the glomerulus in experimental murine nephritis

Renal ageing

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