Follistatin, an activin antagonist, ameliorates renal interstitial fibrosis in a rat model of unilateral ureteral obstruction.
Follistatin, an activin antagonist, ameliorates renal interstitial fibrosis in a rat model of unilateral ureteral obstruction.
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DOI：
10.1155/2014/376191
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发表时间：
2014
影响因子：
--
通讯作者：
Nojima Y
中科院分区：
文献类型：
--
作者：
Maeshima A;Mishima K;Yamashita S;Nakasatomi M;Miya M;Sakurai N;Sakairi T;Ikeuchi H;Hiromura K;Hasegawa Y;Kojima I;Nojima Y
活化素是TGF-β超家族的成员，调节各种细胞类型中的细胞生长和分化。激活素A作为肾发育以及肾损伤后肾小管再生的负调节剂。然而，激活素A是否参与肾纤维化仍不清楚。为了阐明这一问题，我们采用了单侧输尿管梗阻（UUO）大鼠模型。与对侧肾脏相比，UUO肾脏中激活素A的表达显著增加。激活素A在正常肾脏肾小球系膜细胞和间质成纤维细胞中被检测到。在UUO肾脏中，激活素A在间质α-SMA阳性肌成纤维细胞中大量表达。重组卵泡抑素，一种激活素拮抗剂的管理，减少了UUO肾脏的纤维化面积。卵泡抑素处理的肾脏中，肾小管中增殖细胞的数量显著降低，而肾小管中的增殖细胞数量则没有降低。在卵泡抑素处理的肾脏中，α-SMA的表达、I型胶原和纤连蛋白的沉积以及CD 68阳性巨噬细胞浸润显著受到抑制。这些数据表明，激活素A产生的间质成纤维细胞作为一个有效的促纤维化因子在肾纤维化。阻断激活素A的作用可能是预防肾纤维化进展的一种新方法。
Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO). The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.
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影响因子：
24.5
作者：
Ohnishi, N;Miyata, T;Sugano, K
通讯作者：
Sugano, K
影响因子：
--
作者：
Ota, F;Maeshima, A;Nojima, Y
通讯作者：
Nojima, Y
DOI：
10.1164/rccm.200412-1620oc
发表时间：
2005-09-15
影响因子：
24.7
作者：
Aoki, F;Kurabayashi, M;Kojima, I
通讯作者：
Kojima, I
影响因子：
56.9
作者：
NAKAMURA, T;TAKIO, K;SUGINO, H
通讯作者：
SUGINO, H
影响因子：
29.4
作者：
Sugiyama, M;Ichida, T;Asakura, H
通讯作者：
Asakura, H