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Interstitial pericytes decrease in aged mouse kidneys.

Stefanska A, Eng D, Kaverina N, Duffield JS, Pippin JW, Rabinovitch P, Shankland SJ - Aging (Albany NY) (2015)

Bottom Line: This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes.This decrease was more pronounced in the medulla.These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.

ABSTRACT
With increasing age, the kidney undergoes characteristic changes in the glomerular and tubulo-interstitial compartments, which are ultimately accompanied by reduced kidney function. Studies have shown age-related loss of peritubular vessels. Normal peritubular vessel tone, function and survival depend on neighboring pericytes. Pericyte detachment leads to vascular damage, which can be accompanied by their differentiation to fibroblasts and myofibroblasts, a state that favors matrix production. To better understand the fate of pericytes in the aged kidney, 27 month-old mice were studied. Compared to 3 month-old young adult mice, aged kidneys showed a substantial decrease in capillaries, identified by CD31 staining, in both cortex and medulla. This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes. This decrease was more pronounced in the medulla. Capillaries devoid of pericytes were typically dilated in aged mice. Aged kidneys were also characterized by interstitial fibrosis due to increased collagen-I and -III staining. This was accompanied by an increase in the number of pericytes that acquired a pro-fibrotic phenotype, identified by increased PDGFRβ+ / αSMA+ staining. These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis.

No MeSH data available.


Related in: MedlinePlus

Accumulation of type I and III collagen in aged kidneysPicrosirius Red staining of collagen I and III was examined by polarized light microscopy. Additionally, collagen III fibers are visualized with specific antibody (red color), nuclei are labeled with dapi (blue color). (A) Collagen fibers were sparse in the cortex of young adult kidneys. (B) Aged kidneys demonstrated interstitial collagen deposition (arrows indicate examples) in the peritubular and periglomerular area (glomeruli are indicated by asterix). Adventitia of arterial wall was enriched in collagen (arrowhead). (C) Collagen III staining confirms the location of interstitial and periglomerular fibrosis. (D) Picrosirius Red was barely detected in the medulla of young adult kidneys. (E) Picrosirius Red staining was markedly increased in the medulla of aged mice (arrows indicate examples) in the interstitium. (F) Collagen III staining confirms tubulointerstital fibrosis. (G) Graph of quantitation: Picrosirius Red staining significantly increased in the interstitium in both the cortex and the medulla of aged mice. Data are represented as mean ± SEM (n=6).
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Figure 2: Accumulation of type I and III collagen in aged kidneysPicrosirius Red staining of collagen I and III was examined by polarized light microscopy. Additionally, collagen III fibers are visualized with specific antibody (red color), nuclei are labeled with dapi (blue color). (A) Collagen fibers were sparse in the cortex of young adult kidneys. (B) Aged kidneys demonstrated interstitial collagen deposition (arrows indicate examples) in the peritubular and periglomerular area (glomeruli are indicated by asterix). Adventitia of arterial wall was enriched in collagen (arrowhead). (C) Collagen III staining confirms the location of interstitial and periglomerular fibrosis. (D) Picrosirius Red was barely detected in the medulla of young adult kidneys. (E) Picrosirius Red staining was markedly increased in the medulla of aged mice (arrows indicate examples) in the interstitium. (F) Collagen III staining confirms tubulointerstital fibrosis. (G) Graph of quantitation: Picrosirius Red staining significantly increased in the interstitium in both the cortex and the medulla of aged mice. Data are represented as mean ± SEM (n=6).

Mentions: Additionally, Picrosirius Red staining for collagens I and III [31] was performed. Polarized light microscopy was used to visualize and distinguish the thick, strongly birefringent, yellow/red fibers as collagen type I and the thin, weak birefringent, greenish fibers as collagen III [32]. In young adult mouse kidneys, Picrosirius Red staining was very faint. Occasional fibers of collagen III were detected (Figure 2A). In aged kidneys, Picrosirius Red positive staining was increased in the interstitium (i.e. between tubules), and periglomerular areas. In contrast, Picrosirius red staining was not detected within glomeruli (asterix, Figure 2B). Additionally, collagen fibers were present in the adventitia of large blood vessels (arrowhead, Figure 2B). Collagen III immuno-staining confirmed that tubulointerstitial and periglo-merular fibrosis characteristic of the aged kidney (Figure 2C). The percentage of area stained for Picrosirius Red was significantly higher in the aged kidney cortex compared to young adult mice (0.96±0.13% vs. 0.13±0.02% p<0.0001) (arrows, Figure 2, B and G).


Interstitial pericytes decrease in aged mouse kidneys.

Stefanska A, Eng D, Kaverina N, Duffield JS, Pippin JW, Rabinovitch P, Shankland SJ - Aging (Albany NY) (2015)

Accumulation of type I and III collagen in aged kidneysPicrosirius Red staining of collagen I and III was examined by polarized light microscopy. Additionally, collagen III fibers are visualized with specific antibody (red color), nuclei are labeled with dapi (blue color). (A) Collagen fibers were sparse in the cortex of young adult kidneys. (B) Aged kidneys demonstrated interstitial collagen deposition (arrows indicate examples) in the peritubular and periglomerular area (glomeruli are indicated by asterix). Adventitia of arterial wall was enriched in collagen (arrowhead). (C) Collagen III staining confirms the location of interstitial and periglomerular fibrosis. (D) Picrosirius Red was barely detected in the medulla of young adult kidneys. (E) Picrosirius Red staining was markedly increased in the medulla of aged mice (arrows indicate examples) in the interstitium. (F) Collagen III staining confirms tubulointerstital fibrosis. (G) Graph of quantitation: Picrosirius Red staining significantly increased in the interstitium in both the cortex and the medulla of aged mice. Data are represented as mean ± SEM (n=6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4505164&req=5

Figure 2: Accumulation of type I and III collagen in aged kidneysPicrosirius Red staining of collagen I and III was examined by polarized light microscopy. Additionally, collagen III fibers are visualized with specific antibody (red color), nuclei are labeled with dapi (blue color). (A) Collagen fibers were sparse in the cortex of young adult kidneys. (B) Aged kidneys demonstrated interstitial collagen deposition (arrows indicate examples) in the peritubular and periglomerular area (glomeruli are indicated by asterix). Adventitia of arterial wall was enriched in collagen (arrowhead). (C) Collagen III staining confirms the location of interstitial and periglomerular fibrosis. (D) Picrosirius Red was barely detected in the medulla of young adult kidneys. (E) Picrosirius Red staining was markedly increased in the medulla of aged mice (arrows indicate examples) in the interstitium. (F) Collagen III staining confirms tubulointerstital fibrosis. (G) Graph of quantitation: Picrosirius Red staining significantly increased in the interstitium in both the cortex and the medulla of aged mice. Data are represented as mean ± SEM (n=6).
Mentions: Additionally, Picrosirius Red staining for collagens I and III [31] was performed. Polarized light microscopy was used to visualize and distinguish the thick, strongly birefringent, yellow/red fibers as collagen type I and the thin, weak birefringent, greenish fibers as collagen III [32]. In young adult mouse kidneys, Picrosirius Red staining was very faint. Occasional fibers of collagen III were detected (Figure 2A). In aged kidneys, Picrosirius Red positive staining was increased in the interstitium (i.e. between tubules), and periglomerular areas. In contrast, Picrosirius red staining was not detected within glomeruli (asterix, Figure 2B). Additionally, collagen fibers were present in the adventitia of large blood vessels (arrowhead, Figure 2B). Collagen III immuno-staining confirmed that tubulointerstitial and periglo-merular fibrosis characteristic of the aged kidney (Figure 2C). The percentage of area stained for Picrosirius Red was significantly higher in the aged kidney cortex compared to young adult mice (0.96±0.13% vs. 0.13±0.02% p<0.0001) (arrows, Figure 2, B and G).

Bottom Line: This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes.This decrease was more pronounced in the medulla.These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.

ABSTRACT
With increasing age, the kidney undergoes characteristic changes in the glomerular and tubulo-interstitial compartments, which are ultimately accompanied by reduced kidney function. Studies have shown age-related loss of peritubular vessels. Normal peritubular vessel tone, function and survival depend on neighboring pericytes. Pericyte detachment leads to vascular damage, which can be accompanied by their differentiation to fibroblasts and myofibroblasts, a state that favors matrix production. To better understand the fate of pericytes in the aged kidney, 27 month-old mice were studied. Compared to 3 month-old young adult mice, aged kidneys showed a substantial decrease in capillaries, identified by CD31 staining, in both cortex and medulla. This was accompanied by a marked decrease in surrounding NG2+ / PDGFRβ+ pericytes. This decrease was more pronounced in the medulla. Capillaries devoid of pericytes were typically dilated in aged mice. Aged kidneys were also characterized by interstitial fibrosis due to increased collagen-I and -III staining. This was accompanied by an increase in the number of pericytes that acquired a pro-fibrotic phenotype, identified by increased PDGFRβ+ / αSMA+ staining. These findings are consistent with the decline in kidney interstitial pericytes as a critical step in the development of changes to the peritubular vasculature with aging, and accompanying fibrosis.

No MeSH data available.


Related in: MedlinePlus