Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11029-34. doi: 10.1073/pnas.1217308110. Epub 2013 Jun 17.
Wound healing is essential for survival. We took advantage of the Xenopus embryo, which exhibits remarkable capacities to repair wounds quickly and efficiently, to investigate the mechanisms responsible for wound healing. Previous work has shown that injury triggers a rapid calcium response, followed by the activation of Ras homolog (Rho) family guanosine triphosphatases (GTPases), which regulate the formation and contraction of an F-actin purse string around the wound margin. How these processes are coordinated following wounding remained unclear. Here we show that inositol-trisphosphate 3-kinase B (Itpkb) via its enzymatic product inositol 1,3,4,5-tetrakisphosphate (InsP4) plays an essential role during wound healing by modulating the activity of Rho family GTPases and F-actin ring assembly. Furthermore, we show that Itpkb and InsP4 modulate the speed of the calcium wave, which propagates from the site of injury into neighboring uninjured cells. Strikingly, both overexpression of itpkb and exogenous application of InsP4 accelerate the speed of wound closure, a finding that has potential implications in our quest to find treatments that improve wound healing in patients with acute or chronic wounds.
伤口愈合对于生存至关重要。我们利用爪蟾胚胎，它具有快速有效地修复伤口的显著能力，来研究负责伤口愈合的机制。先前的工作表明，损伤会引发快速的钙反应，随后 Ras 同源物（Rho）家族鸟苷三磷酸酶（GTPases）被激活，这些酶调节伤口边缘周围 F-肌动蛋白荷包缝线的形成和收缩。受伤后这些过程如何协调仍不清楚。在这里，我们表明肌醇三磷酸酶 B (Itpkb) 通过其酶产物肌醇 1,3,4,5-四磷酸 (InsP4) 在伤口愈合过程中发挥重要作用，通过调节 Rho 家族 GTPases 和 F-肌动蛋白环组装来调节其活性。此外，我们表明 Itpkb 和 InsP4 调节钙波的速度，钙波从损伤部位传播到相邻的未受伤细胞。引人注目的是，过度表达 itpkb 和外源应用 InsP4 都能加速伤口闭合的速度，这一发现可能对我们寻找治疗急性或慢性伤口患者的伤口愈合的方法有潜在意义。
