Endothelial Insulin-Like Growth Factor-1 Modulates Proliferation and Phenotype of Smooth Muscle Cells Induced by Low Shear Stress
Endothelial Insulin-Like Growth Factor-1 Modulates Proliferation and Phenotype of Smooth Muscle Cells Induced by Low Shear Stress
复制标题
内皮胰岛素样生长因子-1 调节低剪切应力诱导的平滑肌细胞的增殖和表型
DOI：
10.1007/s10439-013-0957-5
复制
发表时间：
2014-04-01
影响因子：
3.8
通讯作者：
Jiang, Zong-Lai
中科院分区：
文献类型：
--
作者：
Wang, Lu;Han, Yue;Jiang, Zong-Lai
内皮细胞（ECs）直接暴露在剪切应力下，调节邻近的血管平滑肌细胞（VSMCs），在动脉粥样硬化过程中血管重构中起重要作用。我们之前的研究发现胰岛素样生长因子（IGFs）可能参与了低剪切应力（LowSS）诱导的血管重构，这一机制尚待阐明。采用EC/VSMC共培养平行板流室，施加低剪应力（5 dyn/cm2）和法向剪应力（NSS, 15 dyn/cm2）作为对照。LowSS诱导ECs分泌IGF-1，随后使共培养VSMCs上的IGF-1受体（IGF-1R）磷酸化，进而增加Akt磷酸化和Sirt2表达。通过RNA干扰（RNAi）降低ECs中的IGF-1逆转了这些对VSMCs的影响。外源性IGF-1增加了IGF-1R和Akt磷酸化、Sirt2表达和VSMCs的增殖，诱导VSMCs向合成表型发展。pi3k /Akt特异性抑制剂wortmannin降低了VSMCs的Sirt2表达、增殖和合成表型转化，但对IGF-1R没有影响。Sirt2 RNAi抑制VSMC增殖和表型转化，但对IGF-1R和Akt无影响。综上所述，LowSS诱导ECs分泌IGF-1，进而旁分泌影响共培养VSMCsviaIGF-1R和Akt的磷酸化以及Sirt2的表达，从而导致细胞增殖和合成表型转化。
Endothelial cells (ECs) are directly exposed to shear stress and modulate the neighboring vascular smooth muscle cells (VSMCs), which plays important roles in vascular remodeling during atherosclerosis. Our previous research revealed that insulin-like growth factors (IGFs) might participate in low shear stress (LowSS) induced vascular remodeling, which remains to be elucidated. Using EC/VSMC co-cultured parallel-plate flow chamber, LowSS (5 dyn/cm2) was applied and normal shear stress (NSS, 15 dyn/cm2) was used as control. LowSS induced IGF-1 secretion from ECs, which subsequently phosphorylated IGF-1 receptor (IGF-1R) on co-cultured VSMCs, then increased Akt phosphorylation and Sirt2 expression. Decreasing IGF-1 in ECs by RNA interference (RNAi) reversed these effects on VSMCs. Exogenous IGF-1 increased IGF-1R and Akt phosphorylation, Sirt2 expression, and proliferation of VSMCs, and induced VSMCs towards synthetic phenotype. PI3 K/Akt specific inhibitor wortmannin decreased Sirt2 expression, proliferation, and synthetic phenotype transformation of VSMCs, but had no effect on IGF-1R. Sirt2 RNAi repressed VSMC proliferation and phenotypic transformation, but had no effect on IGF-1R and Akt. Taken together, LowSS induces the secretion of IGF-1 from ECs, which subsequently paracrine influences the co-cultured VSMCsviaIGF-1R and Akt phosphorylation, and Sirt2 expression, then results in the proliferation and synthetic phenotype transformation.