Leptin activates RhoA/ROCK pathway to induce cytoskeleton remodeling in nucleus pulposus cells.
Leptin activates RhoA/ROCK pathway to induce cytoskeleton remodeling in nucleus pulposus cells.
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瘦素激活 RhoA/ROCK 通路诱导髓核细胞骨架重塑
DOI：
10.3390/ijms15011176
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发表时间：
2014-01-16
影响因子：
5.6
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Li Z;Liang J;Wu WK;Yu X;Yu J;Weng X;Shen J
高瘦素血症与肥胖相关的腰椎间盘退变有关。然而，瘦素对髓核细胞内信号传导的影响尚不清楚。目前的研究试图描绘可能参与的RhoA/ROCK途径瘦素介导的细胞骨架重组髓核细胞。用10 ng/mL的瘦素处理从脊柱侧凸患者分离的髓核细胞。荧光共振能量转移分析用于确定髓核细胞中RhoA信号传导的激活。Western blot分析LIMK 1和cofilin-2蛋白表达。F-肌动蛋白的细胞骨架重组进行了评估罗丹明共轭鬼笔环肽免疫沉淀。瘦素诱导的F-肌动蛋白重组和应力纤维形成髓核细胞，伴随着本地化的RhoA激活和磷酸化的LIMK 1和cofilin。RhoA抑制剂C3外切酶或ROCK抑制剂Y-27632有效地减弱了瘦素对F-肌动蛋白重组和应力纤维形成的影响。这两种抑制剂也阻止了瘦素诱导的LIMK 1和cofilin-2的磷酸化。我们的研究表明，瘦素激活RhoA/ROCK/LIMK/cofilin-2级联反应，诱导髓核细胞骨架重组。这些发现可能为肥胖相关腰椎间盘退变的发病机制提供新的见解。
Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration. Nevertheless, the effect of leptin on the intracellular signaling of nucleus pulposus cells is not clear. The current study sought to delineate the possible involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance energy transfer analysis was used to determine the activation of RhoA signaling in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were analyzed by western blot analysis. F-actin cytoskeletal reorganization was assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F-actin reorganization and stress fiber formation in nucleus pulposus cells, accompanied by localized RhoA activation and phosphorylation of LIMK1 and cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently attenuated the effects of leptin on F-actin reorganization and stress fiber formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1 and cofilin-2. Our study demonstrated that leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus pulposus cells. These findings may provide novel insights into the pathogenic mechanism of obesity-associated lumbar disc degeneration.
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DOI：
10.1590/s1807-59322008000500014
发表时间：
2008-10
期刊：
Clinics (Sao Paulo, Brazil)
影响因子：
--
作者：
Ozenoglu A;Balci H;Ugurlu S;Caglar E;Uzun H;Sarkis C;Gunay C;E EE
通讯作者：
E EE
影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
影响因子：
3.9
作者：
Li, S.;Duance, V. C.;Blain, E. J.
通讯作者：
Blain, E. J.
影响因子：
5.5
作者：
Thirone, Ana C. P.;Speight, Pam;Kapus, Andras
通讯作者：
Kapus, Andras
影响因子：
3.7
作者：
Eichorst JP;Lu S;Xu J;Wang Y
通讯作者：
Wang Y