Stefanska Ania, Eng Diana, Kaverina Natalya, Duffield Jeremy S, Pippin Jeffrey W, Rabinovitch Peter, Shankland Stuart J
Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
Biogen Idec, Cambridge, MA 02142, USA.
Aging (Albany NY). 2015 Jun;7(6):370-82. doi: 10.18632/aging.100756.
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.
随着年龄的增长,肾脏在肾小球和肾小管间质部分会发生特征性变化,最终伴随着肾功能的减退。研究表明,与年龄相关的肾小管周围血管会减少。正常的肾小管周围血管张力、功能和存活依赖于相邻的周细胞。周细胞脱离会导致血管损伤,这可能伴随着它们分化为成纤维细胞和平滑肌成纤维细胞,这种状态有利于基质产生。为了更好地了解老年肾脏中周细胞的命运,对27月龄的小鼠进行了研究。与3月龄的年轻成年小鼠相比,老年肾脏皮质和髓质中经CD31染色鉴定的毛细血管数量大幅减少。同时,周围NG2+ / PDGFRβ+周细胞显著减少。这种减少在髓质中更为明显。在老年小鼠中,缺乏周细胞的毛细血管通常会扩张。老年肾脏还表现为由于I型和III型胶原蛋白染色增加导致的间质纤维化。同时,通过增加的PDGFRβ+ / αSMA+染色鉴定,获得促纤维化表型的周细胞数量增加。这些发现与肾脏间质周细胞的减少一致,这是随着年龄增长肾小管周围血管系统变化及伴随纤维化发展的关键步骤。