N-acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1β-mediated matrix metalloproteinase activation in cardiac fibroblasts.
N-acetyl-Ser-Asp-Lys-Pro inhibits interleukin-1β-mediated matrix metalloproteinase activation in cardiac fibroblasts.
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N-乙酰基-Ser-Asp-Lys-Pro 抑制心脏成纤维细胞中白细胞介素 1β 介导的基质金属蛋白酶活化。
DOI：
10.1007/s00424-013-1262-8
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发表时间：
2013-10
影响因子：
4.5
通讯作者：
Carretero, Oscar A.
中科院分区：
文献类型：
--
作者：
Rhaleb, Nour-Eddine;Pokharel, Saraswati;Sharma, Umesh C.;Peng, Hongmei;Peterson, Edward;Harding, Pamela;Yang, Xiao-Ping;Carretero, Oscar A.
关键词：
心肌基质周转涉及胶原蛋白合成和降解之间的动态平衡，这是由基质金属蛋白酶（MMP）调节的。 N-乙酰基-Ser-Asp-Lys-Pro (Ac-SDKP) 是一种抑制心脏炎症和纤维化的小肽。然而，其在 MMP 调节中的作用尚不清楚。因此，我们假设 Ac-SDKP 促进心脏成纤维细胞中 MMP 的活化，并通过这种机制减少胶原沉积。为此，我们测试了 Ac-SDKP 对白细胞介素 1β (IL-1β；5 ng/ml) 刺激的成年大鼠心脏成纤维细胞的影响。我们测量了总胶原酶活性、MMP-2、MMP-9 和 MMP-13 表达，以及它们的抑制剂、金属蛋白酶组织抑制剂 (TIMP)-1 和 TIMP-2 的活性。为了检查 Ac-SDKP 对控制 MMP 转录的信号通路的影响，我们还测量了核因子-κB (NFκB) 和 p42/44 丝裂原激活蛋白激酶 (MAPK) 的激活。在基础条件下，Ac-SDKP 不会改变心脏成纤维细胞中的胶原酶或明胶酶活性，但会减弱 IL-1β 诱导的总胶原酶活性的增加。同样，Ac-SDKP 使 IL-1β 介导的 MMP-2 和 MMP-9 活性以及 MMP-13 表达增加正常化。 Ac-SDKP 对 MMP 的抑制与 TIMP-1 和 TIMP-2 表达增加相关。胶原蛋白的产生不受 Ac-SDKP、IL-1β 或两种药物的组合的影响。 Ac-SDKP 阻断心肌成纤维细胞中 IL-1β 诱导的 p42/44 磷酸化和 NFκB 激活。我们得出结论，Ac-SDKP 抑制的胶原酶表达和激活与 TIMP-1 和 TIMP-2 表达增加相关。 Ac-SDKP 的这些药理作用可能与抑制 MAPK 和 NFκB 通路有关。
Myocardial matrix turnover involves a dynamic balance between collagen synthesis and degradation, which is regulated by matrix metalloproteinases (MMPs). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) is a small peptide that inhibits cardiac inflammation and fibrosis. However, its role in MMP regulation is not known. Thus, we hypothesized that Ac-SDKP promotes MMP activation in cardiac fibroblasts and decreases collagen deposition via this mechanism. To that end, we tested the effects of Ac-SDKP on interleukin-1β (IL-1β; 5 ng/ml)-stimulated adult rat cardiac fibroblasts. We measured total collagenase activity, MMP-2, MMP-9, and MMP-13 expressions, and activity along with their inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. In order to examine the effects of Ac-SDKP on the signaling pathway that controls MMP transcription, we also measured nuclear factor-κB (NFκB) and p42/44 mitogen-activated protein kinase (MAPK) activation. Ac-SDKP did not alter collagenase or gelatinase activity in cardiac fibroblasts under basal conditions, but blunted the IL-1β-induced increase in total collagenase activity. Similarly, Ac-SDKP normalized the IL-1β-mediated increase in MMP-2 and MMP-9 activities and MMP-13 expression. Inhibition of MMPs by Ac-SDKP was associated with increased TIMP-1 and TIMP-2 expressions. Collagen production was not affected by Ac-SDKP, IL-1β, or a combination of both agents. Ac-SDKP blocked IL-1β-induced p42/44 phosphorylation and NFκB activation in cardiac fibroblasts. We concluded that the Ac-SDKP-inhibited collagenase expression and activation was associated with increased expression of TIMP-1 and TIMP-2. These pharmacological effects of Ac-SDKP may be linked to the inhibition of MAPK and NFκB pathway.
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影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
8.3
作者：
Peng, HM;Carretero, OA;Rhaleb, NE
通讯作者：
Rhaleb, NE
DOI：
10.1152/ajprenal.00421.2004
发表时间：
2005-08-01
影响因子：
4.2
作者：
Liclican, EL;McGiff, JC;Carroll, MA
通讯作者：
Carroll, MA
DOI：
10.1073/pnas.94.15.8121
发表时间：
1997-07-22
影响因子：
11.1
作者：
DAngelo, DD;Sakata, Y;Dorn, GW
通讯作者：
Dorn, GW
DOI：
10.1152/ajprenal.00239.2002
发表时间：
2003-03-01
影响因子：
4.2
作者：
Cheng, MK;McGiff, JC;Carroll, MA
通讯作者：
Carroll, MA