cIAP1 attenuates shear stress-induced hBMSC apoptosis for tissue-engineered blood vessels through the inhibition of the mitochondrial apoptosis pathway
cIAP1 attenuates shear stress-induced hBMSC apoptosis for tissue-engineered blood vessels through the inhibition of the mitochondrial apoptosis pathway
复制标题
cIAP1 通过抑制线粒体凋亡途径来减弱剪切应力诱导的组织工程血管 hBMSC 凋亡
DOI：
10.1016/j.lfs.2015.07.011
复制
发表时间：
2015
期刊：
影响因子：
6.1
通讯作者：
Yi Wei
中科院分区：
文献类型：
--
作者：
Zhao Dajun;Sun Yang;Wei Xufeng;Liang Hongliang;Zhao Lin;Dong Xiaochao;Chen Hao;Chen Wenhao;Yang Jian;Wang Xiaowu;Gao Feng;Yi Wei
AimsShear stress-induced apoptosis is one of the leading problems in seeding cells of tissue-engineered blood vessels (TEBVs). We aim to determine the human bone mesenchymal stem cell (hBMSC) apoptosis under shear stress and its possible mechanism.Main methodshBMSCs were subjected to 3-, 10-, and 30-dyn/cm2shear stress in vitro. Cell multiplication and apoptosis were analyzed by flow cytometry. Apoptosis-related genes were screened by a microarray and evidenced by real-time polymerase chain reaction (RT-PCR). hBMSCs were treated with the human recombinant cell inhibitor of apoptosis protein 1 (cIAP1) and its inhibitor, direct IAP-binding protein with low pl (DIABLO), and then cell apoptosis was analyzed.Key findingsExposure to shear stress (3 dyn/cm2for > 6 h) activated apoptosis progress of hBMSCs. However, the same degree of shear stress (3 dyn/cm2for 6 h) did not induce apoptosis. Microarray screening and RT-PCR revealed that Bcl-2-related ovarian killer (BOK) and apoptotic protease-activating factor 1 (APAF1), key molecules of the mitochondrial apoptosis pathway, were markedly upregulated under 3-dyn/cm2shear stress. Then, we observed that cIAP1, a Caspase 9 inhibitor, was elevated under 3 dyn/cm2at short-time exposure (2 or 6 h), and it was reduced at long-time exposure (24 h). When treated with human recombinant cIAP1, Caspase 3 activity and LDH release of hBMSCs were decreased, and vice versa when treated with DIABLO.SignificancecIAP1 attenuates hBMSC apoptosis when cells were exposed to shear stress through the regulation of the BOK–APAF1–Caspase 9–Caspase 3 pathway. It may present a pharmacological target to enhance hBMSC biological function in the application of TEBVs.
