Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome.
Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome.
复制标题
轻度电刺激和热休克可改善阿尔波特综合征小鼠模型中进行性蛋白尿和肾脏炎症。
DOI：
10.1371/journal.pone.0043852
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kai H
中科院分区：
文献类型：
--
作者：
Koga T;Kai Y;Fukuda R;Morino-Koga S;Suico MA;Koyama K;Sato T;Shuto T;Kai H
Alport综合征是一种遗传性肾小球疾病，伴有蛋白尿和肾炎，由肾小球基底膜IV型胶原编码基因缺陷引起。所有男性和大多数女性患者都会发展为终末期肾病。阻止或减缓蛋白尿和肾炎进展的有效治疗仍在调查中。在这里，我们显示了轻度电应激(MES)和热应激(HS)的联合治疗可以改善Alport综合征小鼠模型的进行性蛋白尿和肾脏损伤。MES+HS可抑制肾损伤标志物中性粒细胞明胶酶相关Lipocalin和促炎细胞因子IL-6、肿瘤坏死因子-α和IL-1β的表达。MES+HS的抗蛋白尿作用是通过激活依赖于热休克蛋白72(HSP72)的磷脂酰肌醇3-羟基激酶(PI3K)-Akt和热休克蛋白72(HSP72)途径实现的。MES+HS的抗炎作用是通过激活肾小球c-jun氨基末端激酶1/2(JNK1/2)和p38依赖的途径实现的。总之，我们的研究表明，MES和HS的联合治疗可能通过激活多个信号通路，包括PI3K-Akt、Hsp72、JNK1/2和p38通路，赋予Alport小鼠抗蛋白尿和抗炎作用，为减缓Alport综合征的病理表型进展提供了一种新的候选治疗策略。
Alport syndrome is a hereditary glomerulopathy with proteinuria and nephritis caused by defects in genes encoding type IV collagen in the glomerular basement membrane. All male and most female patients develop end-stage renal disease. Effective treatment to stop or decelerate the progression of proteinuria and nephritis is still under investigation. Here we showed that combination treatment of mild electrical stress (MES) and heat stress (HS) ameliorated progressive proteinuria and renal injury in mouse model of Alport syndrome. The expressions of kidney injury marker neutrophil gelatinase-associated lipocalin and pro-inflammatory cytokines interleukin-6, tumor necrosis factor-α and interleukin-1β were suppressed by MES+HS treatment. The anti-proteinuric effect of MES+HS treatment is mediated by podocytic activation of phosphatidylinositol 3-OH kinase (PI3K)-Akt and heat shock protein 72 (Hsp72)-dependent pathways in vitro and in vivo. The anti-inflammatory effect of MES+HS was mediated by glomerular activation of c-jun NH2-terminal kinase 1/2 (JNK1/2) and p38-dependent pathways ex vivo. Collectively, our studies show that combination treatment of MES and HS confers anti-proteinuric and anti-inflammatory effects on Alport mice likely through the activation of multiple signaling pathways including PI3K-Akt, Hsp72, JNK1/2, and p38 pathways, providing a novel candidate therapeutic strategy to decelerate the progression of patho-phenotypes in Alport syndrome.
登录
查看更多内容
DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B
DOI：
10.1073/pnas.0804954105
发表时间：
2008-08-12
影响因子：
11.1
作者：
Duan, Yi;Gotoh, Nanami;Weinbaum, Sheldon
通讯作者：
Weinbaum, Sheldon
影响因子：
3.8
作者：
Lian, Kai-Cheng;Chuang, Jing-Jing;Sun, Yung-Wei
通讯作者：
Sun, Yung-Wei
DOI：
10.1152/ajprenal.00503.2005
发表时间：
2007-01-01
影响因子：
4.2
作者：
Endemann, Michaela;Bergmeister, Helga;Aufricht, Christoph
通讯作者：
Aufricht, Christoph
影响因子：
3.7
作者：
Morino, Saori;Kondo, Tatsuya;Sasaki, Kazunari;Adachi, Hironori;Suico, Mary Ann;Sekimoto, Erika;Matsuda, Tomoko;Shuto, Tsuyoshi;Araki, Eiichi;Kai, Hirofumi
通讯作者：
Kai, Hirofumi