SIRT1 deacetylates RFX5 and antagonizes repression of collagen type I (COL1A2) transcription in smooth muscle cells.
SIRT1 deacetylates RFX5 and antagonizes repression of collagen type I (COL1A2) transcription in smooth muscle cells.
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SIRT1 使 RFX5 去乙酰化并拮抗平滑肌细胞中 I 型胶原蛋白 (COL1A2) 转录的抑制。
DOI：
10.1016/j.bbrc.2012.10.043
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发表时间：
2012-11
影响因子：
3.1
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Fang MM;Xie WP;Wang H;Xu Y
动脉粥样硬化斑块内血管平滑肌细胞（SMC）胶原蛋白表达减少导致纤维帽变薄，并对斑块破裂构成巨大威胁。阐明抑制胶原蛋白I型（COL 1A 2）基因的机制可能会提供新的解决方案，可以防止破裂引起的并发症。我们以前已经证明，X盒调节因子（RFX 5）结合到COL 1A 2转录起始位点并抑制其转录。在这里，我们报告SIRT 1，NAD依赖性，III类脱乙酰酶，与RFX 5形成复合物。SIRT 1或NAMPT的过度表达，合成NAD+激活SIRT 1，或用SIRT 1激动剂白藜芦醇处理降低RFX 5乙酰化，破坏RFX 5对COL 1A 2启动子活性的抑制。相反，敲低SIRT 1或用SIRT 1抑制剂处理诱导RFX 5乙酰化并增强胶原蛋白转录的抑制。SIRT 1通过促进RFX 5的核排出和蛋白酶体降解来拮抗RFX 5的活性，从而抑制其与COL 1A 2启动子的结合。促炎细胞因子IFN-γ通过下调SMC中SIRT 1的表达来抑制COL 1A 2的转录。因此，我们的数据已经确定了SIRT 1通过调节RFX 5活性来维持SMC中胶原合成的新途径。
Decreased expression of collagen by vascular smooth muscle cells (SMCs) within the atherosclerotic plaque contributes to the thinning of the fibrous cap and poses a great threat to plaque rupture. Elucidation of the mechanism underlying repressed collagen type I (COL1A2) gene would potentially provide novel solutions that can prevent rupture-induced complications. We have previously shown that regulatory factor for X-box (RFX5) binds to theCOL1A2transcription start site and represses its transcription. Here we report that SIRT1, an NAD-dependent, class III deacetylase, forms a complex with RFX5. Over-expression of SIRT1 or NAMPT, which synthesizes NAD+ to activate SIRT1, or treatment with the SIRT1 agonist resveratrol decreases RFX5 acetylation and disrupts repression of theCOL1A2promoter activity by RFX5. On the contrary, knockdown of SIRT1 or treatment with SIRT1 inhibitors induces RFX5 acetylation and enhances the repression of collagen transcription. SIRT1 antagonizes RFX5 activity by promoting its nuclear expulsion and proteasomal degradation hence dampening its binding to theCOL1A2promoter. The pro-inflammatory cytokine IFN-γ repressesCOL1A2transcription by down-regulating SIRT1 expression in SMCs. Therefore, our data have identified as novel pathway whereby SIRT1 maintains collagen synthesis in SMCs by modulating RFX5 activity.
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影响因子：
13.5
作者：
S. Godichaud;S. Krisa;B. Couronné;L. Dubuisson;J. Mérillon;A. Desmoulière;J. Rosenbaum
通讯作者：
S. Godichaud;S. Krisa;B. Couronné;L. Dubuisson;J. Mérillon;A. Desmoulière;J. Rosenbaum
影响因子：
10.5
作者：
BRACHMANN, CB;SHERMAN, JM;BOEKE, JD
通讯作者：
BOEKE, JD
影响因子：
9.8
作者：
Cudmore, Melissa J.;Ramma, Wenda;Ahmed, Asif
通讯作者：
Ahmed, Asif
DOI：
10.1074/jbc.m109.016469
发表时间：
2009-05
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Tong Zhang;Jhoanna G. Berrocal;Kristine M. Frizzell;Matthew J. Gamble;Michelle E. DuMond;Raga Krishnakumar;Tianle Yang;A. Sauve;W. Lee Kraus
通讯作者：
Tong Zhang;Jhoanna G. Berrocal;Kristine M. Frizzell;Matthew J. Gamble;Michelle E. DuMond;Raga Krishnakumar;Tianle Yang;A. Sauve;W. Lee Kraus
影响因子：
3.7
作者：
Dyson OF;Walker LR;Whitehouse A;Cook PP;Akula SM
通讯作者：
Akula SM