Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue.
Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue.
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DOI：
10.1242/bio.026187
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发表时间：
2018-01-17
期刊：
影响因子：
2.4
通讯作者：
Martins-Green M
中科院分区：
文献类型：
--
作者：
Liu Y;Dhall S;Castro A;Chan A;Alamat R;Martins-Green M
伤口愈合是一个复杂的过程，涉及在时间和空间上重叠的连续阶段，并在基因和蛋白质水平上动态地相互影响。我们以前表明，胰岛素通过刺激更快的再生愈合来加速伤口愈合。胰岛素刺激的过程之一是单核细胞/巨噬细胞趋化性的增加。在这项研究中，我们进行了实验，在体内和体外，以阐明参与胰岛素诱导的单核细胞/巨噬细胞趋化性的信号转导途径。我们发现，胰岛素刺激THP-1细胞的趋化性在剂量依赖性和胰岛素受体依赖性的方式。我们还表明，激酶PI 3 K-Akt，SPAK/JNK和p38 MAPK是胰岛素诱导的信号通路中的关键分子，导致THP-1细胞的化学吸引。此外，PI 3 K-Akt和SPAK/JNK信号传导均涉及Rac 1激活，Rac 1是调节细胞运动性的重要分子。事实上，在愈合过程的早期阶段局部应用Rac 1抑制剂会导致愈合延迟和受损，即使在胰岛素存在的情况下也是如此。这些结果描述了涉及胰岛素诱导的单核细胞/巨噬细胞趋化性的细胞和分子机制，这些细胞对适当的愈合至关重要。总结：胰岛素调节多个信号通路，导致单核细胞/巨噬细胞趋化性进入伤口组织，涉及-Akt，SPAK/JNK，和p38 MAPK，这反过来又参与Rac 1激活。此外，这些结果增强了我们对胰岛素调节的伤口炎症反应的理解。
Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing. Summary: Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue, involving -Akt, SPAK/JNK, and p38 MAPK which in turn are involved in Rac1 activation. Furthermore, these results augment our understanding of the insulin-regulated wound inflammatory response.
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影响因子：
3.1
作者：
Leyva-Illades, Dinorah;Cherla, Rama P.;Tesh, Vernon L.
通讯作者：
Tesh, Vernon L.
DOI：
10.1083/jcb.144.6.1337
发表时间：
1999-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Farrelly N;Lee YJ;Oliver J;Dive C;Streuli CH
通讯作者：
Streuli CH
影响因子：
4.3
作者：
Malik, Reshad K. J.;Ghurye, Rohit R.;Stewart, Helen J. S.
通讯作者：
Stewart, Helen J. S.
DOI：
10.1111/apha.12076
发表时间：
2013-04
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Curry FR;Adamson RH
通讯作者：
Adamson RH
影响因子：
5.3
作者：
Liu Y;Petreaca M;Martins-Green M
通讯作者：
Martins-Green M