An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts
An analysis of the effects of stretch on IGF-I secretion from rat ventricular fibroblasts
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DOI：
10.1152/ajpheart.01413.2006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Giles, Wayne R.
中科院分区：
文献类型：
--
作者：
Hu, Betty S.;Landeen, Lee K.;Giles, Wayne R.
机械力可以在心肌中诱导许多基本的短期和长期反应。这些变化包括细胞外基质的改变，细胞信号通路的激活，基因调控的改变，细胞增殖和生长的改变，以及一些多肽和生长因子的分泌。现在已经知道，许多这种自分泌/旁分泌因子是由心肌细胞和心室成纤维细胞(CFB)在拉伸时分泌的。其中一种物质是IGF-I。IGF-I是一种重要的自分泌/旁分泌因子，可调节肥大等生理或病理生理反应。在这项研究中，我们研究了机械扰动，双轴应变，对成年大鼠CFB分泌IGF-I的可能影响。CFB在24小时内接受静态拉伸(3-10%)或循环拉伸(10%；0.1-1赫兹)。用ELISA法测定条件培养液中IGF-I的浓度，检测CFB对选择的拉伸模式的IGF-I分泌。静态拉伸没有导致CFB分泌IGF-I的任何可测量的调节。然而，与非拉伸对照组相比，循环拉伸显著增加CFB分泌IGF-I的频率和时间依赖关系。这种牵张引起的分泌增加对细胞外[Ca~(2+)]的变化或L型钙通道的阻断相对不敏感。相反，肌浆网(Endo)钙ATPase抑制剂thapsigargin显著减少牵张诱导的CFB分泌IGF-I。我们进一步证明IGF-I可以上调心肌细胞心钠素的mRNA表达。综上所述，周期性拉伸可以显著增加CFB分泌IGF-I，这种作用依赖于thapsigargin敏感的细胞内[Ca~(2+)]池。
Mechanical force can induce a number of fundamental short- and longterm responses in myocardium. These include alterations in ECM, activation of cell-signaling pathways, altered gene regulation, changes in cell proliferation and growth, and secretion of a number of peptides and growth factors. It is now known that a number of these autocrine/ paracrine factors are secreted from both cardiomyocytes and ventricular cardiac fibroblasts (CFb) in response to stretch. One such substance is IGF-I. IGF-I is an important autocrine/paracrine factor that can regulate physiological or pathophysiological responses, such as hypertrophy. In this study, we addressed the possible effects of mechanical perturbation, biaxial strain, on IGF-I secretion from adult rat CFb. CFb were subjected to either static stretch (3-10%) or cyclic stretch (10%; 0.1-1 Hz) over a 24-h period. IGF-I secretion from CFb in response to selected stretch paradigms was examined using ELISA to measure IGF-I concentrations in conditioned media. Static stretch did not result in any measurable modulation of IGF-I secretion from CFb. However, cyclic stretch significantly increased IGF-I secretion from CFb in a frequency- and time-dependent manner compared with nonstretched controls. This stretch-induced increase in secretion was relatively insensitive to changes in extracellular [Ca2+] or to block of L-type Ca2+ channels. In contrast, thapsigargin, an inhibitor of sarco(endo) plasmic reticulum Ca2+ ATPase, remarkably decreased stretch-induced IGF-I secretion from CFb. We further show that IGF-I can upregulate mRNA expression of atrial natriuretic peptide in myocytes. In summary, cyclic stretch can significantly increase IGF-I secretion from CFb, and this effect is dependent on a thapsigargin-sensitive pool of intracellular [Ca2+].