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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

A subset of pericytes differentiate into myofibroblasts and increase in aged kidneysPericytes were identified by NG2+/PDGFRß+ staining (blue and green colors respectively). αSMA was used as myofibroblast marker (red color). (A) In the young adult kidney cortex, (B) most pericytes do not express αSMA. However in preglomerular arterioles (C) αSMA expression was present together with NG2/PDGFRß staining. (D) In aged kidney, αSMA increased in pericytes (E) and PDGFRß+ /NG2− cells (F). (G) Medulla of young adult kidney showed the presence αSMA in some peritubular capillaries (H) and contractile vasa recta cells (I). In aged mouse kidney, (J) there was accumulation of αSMA+ cells co-expressing PDGFRß and NG2 (K) or PDGFRß only (L). Quantification of αSMA expression in NG2+ and PDGFRß + cells showed that PDGFRß+ cells outnumber NG2+ cells in both young adult and aged kidneys. There was a dramatic increase in PDGFRß+αSMA+ cells and the numbers of αSMA-cells expressing either PDGFRß or NG2 were significantly lower in both (M) the cortex and (N) the medulla. Data are represented as mean ± SEM (n=6).
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Figure 5: A subset of pericytes differentiate into myofibroblasts and increase in aged kidneysPericytes were identified by NG2+/PDGFRß+ staining (blue and green colors respectively). αSMA was used as myofibroblast marker (red color). (A) In the young adult kidney cortex, (B) most pericytes do not express αSMA. However in preglomerular arterioles (C) αSMA expression was present together with NG2/PDGFRß staining. (D) In aged kidney, αSMA increased in pericytes (E) and PDGFRß+ /NG2− cells (F). (G) Medulla of young adult kidney showed the presence αSMA in some peritubular capillaries (H) and contractile vasa recta cells (I). In aged mouse kidney, (J) there was accumulation of αSMA+ cells co-expressing PDGFRß and NG2 (K) or PDGFRß only (L). Quantification of αSMA expression in NG2+ and PDGFRß + cells showed that PDGFRß+ cells outnumber NG2+ cells in both young adult and aged kidneys. There was a dramatic increase in PDGFRß+αSMA+ cells and the numbers of αSMA-cells expressing either PDGFRß or NG2 were significantly lower in both (M) the cortex and (N) the medulla. Data are represented as mean ± SEM (n=6).

Mentions: Perivascular cells are considered a possible source of kidney fibrosis in chronic kidney injury [28, 29]. In order to determine the subset of pericytes that differentiate into myofibroblast in the aged kidney, pericytes (identified by PDGFRß+, NG2+) were co-stained for αSMA to mark myofibroblasts [36] In young adult kidney cortex (Figure 5A), αSMA staining is occasionally detected in peritubular pericytes (Figure 5B), and always in vascular smooth cells of renal arterioles (Figure 5C). In aged kidney cortex (Figure 5, D), there was an increase of αSMA-expressing pericytes/perivascular cells in regions of tubulointerstitial fibrosis (Figure 5E-F). In the young adult medulla (Figure 5G), most pericytes did not express αSMA (Figure 5H), with the exception of the vasa recta (Figure 5I). In aged kidney, αSMA staining increased substantially (Figure 5J). Overlapping staining for αSMA and pericyte markers was confined to tubulointerstitial fibrosis (Figure 5K-L).


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)

A subset of pericytes differentiate into myofibroblasts and increase in aged kidneysPericytes were identified by NG2+/PDGFRß+ staining (blue and green colors respectively). αSMA was used as myofibroblast marker (red color). (A) In the young adult kidney cortex, (B) most pericytes do not express αSMA. However in preglomerular arterioles (C) αSMA expression was present together with NG2/PDGFRß staining. (D) In aged kidney, αSMA increased in pericytes (E) and PDGFRß+ /NG2− cells (F). (G) Medulla of young adult kidney showed the presence αSMA in some peritubular capillaries (H) and contractile vasa recta cells (I). In aged mouse kidney, (J) there was accumulation of αSMA+ cells co-expressing PDGFRß and NG2 (K) or PDGFRß only (L). Quantification of αSMA expression in NG2+ and PDGFRß + cells showed that PDGFRß+ cells outnumber NG2+ cells in both young adult and aged kidneys. There was a dramatic increase in PDGFRß+αSMA+ cells and the numbers of αSMA-cells expressing either PDGFRß or NG2 were significantly lower in both (M) the cortex and (N) the medulla. Data are represented as mean ± SEM (n=6).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: A subset of pericytes differentiate into myofibroblasts and increase in aged kidneysPericytes were identified by NG2+/PDGFRß+ staining (blue and green colors respectively). αSMA was used as myofibroblast marker (red color). (A) In the young adult kidney cortex, (B) most pericytes do not express αSMA. However in preglomerular arterioles (C) αSMA expression was present together with NG2/PDGFRß staining. (D) In aged kidney, αSMA increased in pericytes (E) and PDGFRß+ /NG2− cells (F). (G) Medulla of young adult kidney showed the presence αSMA in some peritubular capillaries (H) and contractile vasa recta cells (I). In aged mouse kidney, (J) there was accumulation of αSMA+ cells co-expressing PDGFRß and NG2 (K) or PDGFRß only (L). Quantification of αSMA expression in NG2+ and PDGFRß + cells showed that PDGFRß+ cells outnumber NG2+ cells in both young adult and aged kidneys. There was a dramatic increase in PDGFRß+αSMA+ cells and the numbers of αSMA-cells expressing either PDGFRß or NG2 were significantly lower in both (M) the cortex and (N) the medulla. Data are represented as mean ± SEM (n=6).
Mentions: Perivascular cells are considered a possible source of kidney fibrosis in chronic kidney injury [28, 29]. In order to determine the subset of pericytes that differentiate into myofibroblast in the aged kidney, pericytes (identified by PDGFRß+, NG2+) were co-stained for αSMA to mark myofibroblasts [36] In young adult kidney cortex (Figure 5A), αSMA staining is occasionally detected in peritubular pericytes (Figure 5B), and always in vascular smooth cells of renal arterioles (Figure 5C). In aged kidney cortex (Figure 5, D), there was an increase of αSMA-expressing pericytes/perivascular cells in regions of tubulointerstitial fibrosis (Figure 5E-F). In the young adult medulla (Figure 5G), most pericytes did not express αSMA (Figure 5H), with the exception of the vasa recta (Figure 5I). In aged kidney, αSMA staining increased substantially (Figure 5J). Overlapping staining for αSMA and pericyte markers was confined to tubulointerstitial fibrosis (Figure 5K-L).

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