Combating Adaptation to Cyclic Stretching By Prolonging Activation of Extracellular Signal-Regulated Kinase.
Combating Adaptation to Cyclic Stretching By Prolonging Activation of Extracellular Signal-Regulated Kinase.
复制标题
DOI：
10.1007/s12195-013-0289-4
复制
发表时间：
2013-09
影响因子：
2.8
通讯作者：
Tranquillo, Robert T.
中科院分区：
文献类型：
--
作者：
Weinbaum, Justin S.;Schmidt, Jillian B.;Tranquillo, Robert T.
关键词：
在开发基于纤维蛋白支架的细胞重塑的可植入组织中，成功的关键指标是高胶原蛋白含量。细胞胶原蛋白的合成受到周期性拉伸的刺激，但受到细胞适应的限制。适应是由细胞外信号调节激酶（ERK）的失活介导的;因此，抑制ERK失活应改善机械刺激的胶原蛋白产生，并加速强工程组织的发育。本研究的假设是，p38丝裂原活化蛋白激酶（p38）激活的拉伸限制ERK的激活和SB 203580的p38/亚型的化学抑制将增加拉伸诱导的ERK激活和胶原蛋白的产生。p38和ERK都被15分钟的拉伸激活，但只有p38在1小时后保持活性。在使用细胞单层鉴定有效剂量的抑制剂后，发现5 M SB 203580在周期性拉伸的基于纤维蛋白的组织构建体中使ERK活化增加两倍。当将5 M SB 203580添加到暴露于三周递增幅度循环拉伸的构建体的培养基中时，获得了2.6倍更高的拉伸诱导的总胶原。总之，SB 203580避免了对拉伸诱导的胶原蛋白产生的适应，并且可用于机械强度是优先考虑的工程组织。
In developing implantable tissues based on cellular remodeling of a fibrin scaffold, a key indicator of success is high collagen content. Cellular collagen synthesis is stimulated by cyclic stretching but is limited by cellular adaptation. Adaptation is mediated by deactivation of extracellular signal-regulated kinase (ERK); therefore inhibition of ERK deactivation should improve mechanically stimulated collagen production and accelerate the development of strong engineered tissues. The hypothesis of this study is that p38 mitogen activated protein kinase (p38) activation by stretching limits ERK activation and that chemical inhibition of p38/isoforms with SB203580 will increase stretching-induced ERK activation and collagen production. Both p38 and ERK were activated by 15 minutes of stretching but only p38 remained active after 1 hour. After an effective dose of inhibitor was identified using cell monolayers, 5 M SB203580 was found to increase ERK activation by two-fold in cyclically stretched fibrin-based tissue constructs. When 5 M SB203580 was added to the culture medium of constructs exposed to three weeks of incremental amplitude cyclic stretch, 2.6 fold higher stretching-induced total collagen was obtained. In conclusion, SB203580 circumvents adaptation to stretching induced collagen production and may be useful in engineering tissues where mechanical strength is a priority.
登录
查看更多内容
影响因子：
7.3
作者：
Birkenkamp, KU;Tuyt, LML;Vellenga, E
通讯作者：
Vellenga, E
影响因子：
2.2
作者：
DOMBI, GW;HAUT, RC;SULLIVAN, WG
通讯作者：
SULLIVAN, WG
影响因子：
4.8
作者：
Mucsi, I;Skorecki, KL;Goldberg, HJ
通讯作者：
Goldberg, HJ
影响因子：
10.5
作者：
Engel, FB;Schebesta, M;Keating, MT
通讯作者：
Keating, MT
影响因子：
--
作者：
Ponticos, Markella;Holmes, Alan M.;Lindahl, Gisela E.
通讯作者：
Lindahl, Gisela E.