Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation.
Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation.
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DOI：
10.1083/jcb.200704015
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发表时间：
2007-10-08
期刊：
影响因子：
--
通讯作者：
Bianchi ME
中科院分区：
文献类型：
--
作者：
Palumbo R;Galvez BG;Pusterla T;De Marchis F;Cossu G;Marcu KB;Bianchi ME
组织损伤通常伴随着愈合，因为分化的细胞和干细胞都迁移以取代死亡或受损的细胞。成中膜血管细胞（可以修复肌肉的血管相关干细胞）和成纤维细胞向受损组织释放的可溶性因子迁移。两种这样的因子是高迁移率族蛋白1（HMGB 1），一种由经历非程序性死亡（坏死）的细胞释放但不由凋亡细胞释放的核蛋白，以及基质衍生因子（SDF）-1/CXCL12。我们发现HMGB 1通过细胞外信号调节激酶磷酸化激活经典核因子κB（NF-κB）通路。NF-κB信号传导对于HMGB 1和SDF-1/CXCL 12的趋化性是必需的，但对于生长因子血小板衍生生长因子、甲酰-met-leu-phe（一种模拟细菌侵袭的肽）或原型NF-κ B激活信号肿瘤坏死因子α则不是必需的。在营养不良的小鼠中，如果它们的NF-κB信号通路被禁用，则注射到全身循环中的中血管母细胞不能有效地进入肌肉。这些发现表明，NF-κB信号除了在炎症的早期事件控制组织再生。
Tissue damage is usually followed by healing, as both differentiated and stem cells migrate to replace dead or damaged cells. Mesoangioblasts (vessel-associated stem cells that can repair muscles) and fibroblasts migrate toward soluble factors released by damaged tissue. Two such factors are high mobility group box 1 (HMGB1), a nuclear protein that is released by cells undergoing unscheduled death (necrosis) but not by apoptotic cells, and stromal derived factor (SDF)–1/CXCL12. We find that HMGB1 activates the canonical nuclear factor κB (NF-κB) pathway via extracellular signal-regulated kinase phosphorylation. NF-κB signaling is necessary for chemotaxis toward HMGB1 and SDF-1/CXCL12, but not toward growth factor platelet-derived growth factor, formyl-met-leu-phe (a peptide that mimics bacterial invasion), or the archetypal NF-κB–activating signal tumor necrosis factor α. In dystrophic mice, mesoangioblasts injected into the general circulation ingress inefficiently into muscles if their NF-κB signaling pathway is disabled. These findings suggest that NF-κB signaling controls tissue regeneration in addition to early events in inflammation.
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