Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling.
Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling.
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尾加压素 II 通过 JNK-LRP6 信号抑制压力超负荷期间小鼠心脏侧群细胞的增殖
DOI：
10.1111/jcmm.12230
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发表时间：
2014-05
影响因子：
5.3
通讯作者：
Zou Y
中科院分区：
文献类型：
--
作者：
Chen Z;Xu J;Ye Y;Li Y;Gong H;Zhang G;Wu J;Jia J;Liu M;Chen Y;Yang C;Tang Y;Zhu Y;Ge J;Zou Y
心侧群细胞（CSP）作为内在心脏干细胞，是患病心脏再生的有前途的细胞资源。然而，心脏中CSPs的比例相对较低，限制了CSPs在病理生理条件下有效修复心脏、改善心功能的能力。哪些因素限制病变心脏中 CSP 的增殖尚不清楚。在这里，我们发现尾加压素 II (UII) 在压力超负荷期间通过 c-Jun N 末端激酶 (JNK) 和低密度脂蛋白受体相关蛋白 6 (LRP6) 信号传导调节 CSP 的增殖。压力超负荷极大地上调血浆中UII水平，UII受体(UT)拮抗剂urantide，促进CSP增殖并改善慢性压力超负荷期间的心脏功能障碍。在经过机械拉伸 (MS) 的培养 CSP 中，UII 显着抑制 UT 的增殖。纳米流体蛋白质组免疫分析表明，压力过载期间 UII 抑制 CSP 增殖的因素是 JNK 激活，而不是细胞外信号调节激酶信号传导。进一步的体外分析表明，UII 诱导的磷酸化 JNK 调节 MS 后培养的 CSP 中 LRP6 的磷酸化，这对于压力过载期间 UII 对 CSP 的抑制作用很重要。总之，在压力超负荷期间，UII 通过 JNK/LRP6 信号传导抑制 CSP 的增殖。 UII 的药理学抑制可促进小鼠 CSP 增殖，为压力超负荷引起的心力衰竭提供可能的治疗方法。
Cardiac side population cells (CSPs) are promising cell resource for the regeneration in diseased heart as intrinsic cardiac stem cells. However, the relative low ratio of CSPs in the heart limited the ability of CSPs to repair heart and improve cardiac function effectively under pathophysiological condition. Which factors limiting the proliferation of CSPs in diseased heart are unclear. Here, we show that urotensin II (UII) regulates the proliferation of CSPs by c‐Jun N‐terminal kinase (JNK) and low density lipoprotein receptor‐related protein 6 (LRP6) signalling during pressure overload. Pressure overload greatly upregulated UII level in plasma, UII receptor (UT) antagonist, urantide, promoted CSPs proliferation and improved cardiac dysfunction during chronic pressure overload. In cultured CSPs subjected to mechanical stretch (MS), UII significantly inhibited the proliferation by UT. Nanofluidic proteomic immunoassay showed that it is the JNK activation, but not the extracellular signal‐regulated kinase signalling, that involved in the UII‐inhibited‐ proliferation of CSPs during pressure overload. Further analysis in vitro indicated UII‐induced‐phospho‐JNK regulates phosphorylation of LRP6 in cultured CSPs after MS, which is important in the inhibitory effect of UII on the CSPs during pressure overload. In conclusion, UII inhibited the proliferation of CSPs by JNK/LRP6 signalling during pressure overload. Pharmacological inhibition of UII promotes CSPs proliferation in mice, offering a possible therapeutic approach for cardiac failure induced by pressure overload.
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影响因子：
7.3
作者：
Russell, FD;Molenaar, P;O'Brien, DM
通讯作者：
O'Brien, DM
影响因子：
11.8
作者：
Davidson, Gary;Shen, Jinlong;Niehrs, Christof
通讯作者：
Niehrs, Christof
影响因子：
4.9
作者：
Cheung, BMY;Leung, R;Wong, LYF
通讯作者：
Wong, LYF
影响因子：
3.5
作者：
Liang, Simon X.;Tan, Terence Y. L.;Chong, Beng
通讯作者：
Chong, Beng
影响因子：
64.8
作者：
Laugwitz, KL;Moretti, A;Chien, KR
通讯作者：
Chien, KR