TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS.
TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS.
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DOI：
10.1016/j.resp.2011.08.012
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发表时间：
2011-12-15
影响因子：
2.3
通讯作者：
Verin, Alexander D.
中科院分区：
文献类型：
--
作者：
Poirier, Christophe;Gorshkov, Boris A.;Zemskova, Marina A.;Bogatcheva, Natalia V.;Verin, Alexander D.
TIMAP是蛋白磷酸酶1的调控亚基，其作用在很大程度上尚不清楚。我们最近的数据表明TIMAP参与了培养的肺内皮单层屏障功能的调节（Csortos等，Am J Physiol Lung Cell Mol Physiol 295: L440-450, 2008）。本研究表明，TIMAP耗竭会加剧脂多糖（LPS）诱导的小鼠肺血管渗漏，表明TIMAP在体内具有屏障保护作用。Real-Time RT - PCR分析显示，LPS处理显著抑制了Timap mRNA水平。这种抑制不是通过下调Timap启动子活性实现的，这表明LPS降低了Timap mRNA的稳定性。蛋白激酶A （PKA）抑制剂H-89预处理可降低TIMAP mRNA水平，而PKA激活剂bnz-cAMP预处理可提高TIMAP mRNA水平，减轻lps诱导的TIMAP mRNA下降。综上所述，这些数据证实了TIMAP的屏障保护作用，并表明屏障破坏和屏障保护剂可能通过调节TIMAP的表达作为影响屏障通透性的机制。
TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers (Csortos et al., Am J Physiol Lung Cell Mol Physiol 295: L440-450, 2008). Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.
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影响因子：
5.4
作者：
Heinzel, Kornelia;Bleul, Conrad C.
通讯作者：
Bleul, Conrad C.
影响因子：
5.6
作者：
Bogatcheva, Natalia V.;Zemskova, Marina A.;Kovalenkov, Yevgeniy;Poirier, Christophe;Verin, Alexander D.
通讯作者：
Verin, Alexander D.
影响因子：
3
作者：
Okamoto, R;Ito, M;Nakano, T
通讯作者：
Nakano, T
DOI：
10.1016/j.bbrc.2005.10.089
发表时间：
2005-12-23
影响因子：
3.1
作者：
Kim, K;Li, LJ;Ballermann, BJ
通讯作者：
Ballermann, BJ
DOI：
10.1152/ajplung.00325.2007
发表时间：
2008-09-01
影响因子：
4.9
作者：
Csortos, Csilla;Czikora, Istvan;Verin, Alexander D.
通讯作者：
Verin, Alexander D.