Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary epithelial cells
Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary epithelial cells
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DOI：
10.1165/rcmb.2005-0144oc
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发表时间：
2005-09-01
影响因子：
6.4
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Jin, Y;Kim, HP;Choi, AMK
我们已经使用基因表达谱方法在各种肺损伤和人类肺部疾病模型中识别新的分子靶点。在这些研究中显著诱导的许多基因中，富含半胱氨酸的61(Cyr61)一直被列为最重要的基因之一。在这里，我们使用已建立的高氧模型来更好地了解Cyr61在急性肺损伤中的作用。Cyr61是一个应激相关的即刻-早期反应基因，已知具有多种功能，涉及血管生成、肿瘤发生和伤口修复。它属于新发现的含有六种生长调节因子的“CCN”家族。我们在体内发现，高氧可诱导多种肺细胞和肺组织中Cyr61的表达。功能丧失研究，通过siRNA抑制Cyr61的表达，加速了高氧后肺上皮细胞的死亡。功能研究的成果，通过过度表达Cyr61，显著增强了对包括高氧在内的细胞死亡的抵抗力。此外，过表达Cyr61的细胞可诱导Akt激活。通过siRNA抑制Akt可消除Cyr61高表达细胞对高氧的保护作用。综上所述，我们的数据表明，Cyr61的表达在高氧诱导的肺上皮细胞死亡中起到了细胞保护作用，这种作用部分是通过Akt信号通路介导的。
We have used gene expression profiling approaches to identify new molecular targets in various models of lung injury and human lung diseases. Among the many genes that are significantly induced in these studies, cysteine-rich61 (Cyr61) consistently ranks as one of the most significant genes. Here, we use the well-established model of hyperoxia to better understand the function of Cyr61 in acute lung injury. Cyr61, a stress-related immediate-early response gene, has known diverse functions involving angiogenesis, tumorigenesis, and wound repair. It belongs to the newly discovered "CCN" family containing six growth and regulatory factors. We showed that hyperoxia induces Cyr61 expression in a variety of pulmonary cells and in lung tissue in vivo. Loss of function studies, by suppressing Cyr61 expression by siRNA, accelerated lung epithelial cell death after hyperoxia. Gain of function studies, by overexpressing Cyr61, significantly conferred increased resistance to hyperoxia-incluced cell death. Moreover, cells overexpressing Cyr61 induce Akt activation. Inhibition of Akt by siRNA abrogated the protective effects of Cyr61-overexpressing cells in response to hyperoxia. Taken together, our data demonstrate that Cyr61 expression provides cytoprotection in hyperoxia-induced pulmonary epithelial cell death and that this effect was in part mediated via the Akt signaling pathway.