NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.
NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.
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核因子-κB的激活持续到肌腱愈合的重塑阶段，并促进肌成纤维细胞的存活。
DOI：
10.1126/scisignal.abb7209
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发表时间：
2020-11-17
影响因子：
7.3
通讯作者：
Loiselle AE
中科院分区：
文献类型：
--
作者：
Best KT;Nichols AEC;Knapp E;Hammert WC;Ketonis C;Jonason JH;Awad HA;Loiselle AE
虽然在组织修复的早期阶段炎症是必要的，但持续性炎症会导致纤维化。急性肌腱损伤通常通过纤维化机制愈合，这会阻碍再生和功能恢复。由于核因子κB（NF - κB）信号介导的炎症与这一过程有关，我们研究了肌腱愈合过程中经典NF - κB信号的空间、时间以及细胞类型特异性激活情况。在小鼠肌腱愈合的所有阶段，包括重塑阶段，NF - κB信号都持续存在，并且来自硬腱蛋白（Scx）谱系的腱细胞和成肌纤维细胞是在修复后期仍保留NF - κB激活的主要细胞群。我们证实了人肌腱瘢痕组织中的成肌纤维细胞存在持续性NF - κB激活。在小鼠Scx谱系细胞中删除经典的NF - κB激酶IKKβ，会在肌腱修复后期增加细胞凋亡以及基质蛋白 periostin的沉积，这表明持续性NF - κB信号可能促进成肌纤维细胞存活和纤维化进展。与此一致的是，与人对照组织相比，人肌腱瘢痕样本中的成肌纤维细胞显示出增强的促存活信号。总之，这些数据表明NF - κB可能通过炎症依赖和炎症非依赖性功能，如NF - κB介导的细胞存活，促进肌腱纤维化愈合。
Although inflammation is necessary during the early phases of tissue repair, persistent inflammation contributes to fibrosis. Acute tendon injuries often heal through a fibrotic mechanism, which impedes regeneration and functional recovery. Because inflammation mediated by nuclear factor κB (NF-κB) signaling is implicated in this process, we examined the spatial, temporal, and cell type–specific activation profile of canonical NF-κB signaling during tendon healing. NF-κB signaling was maintained through all phases of tendon healing in mice, including the remodeling phase, and tenocytes and myofibroblasts from the Scleraxis (Scx)- lineage were the predominant populations that retained NF-κB activation into the late stages of repair. We confirmed persistent NF-κB activation in myofibroblasts in human tendon scar tissue. Deleting the canonical NF-κB kinase, IKKβ, in Scx-lineage cells in mice increased apoptosis and the deposition of the matrix protein periostin during the late stages of tendon repair, suggesting that persistent NF-κB signaling may facilitate myofibroblast survival and fibrotic progression. Consistent with this, myofibroblasts in human tendon scar samples displayed enhanced prosurvival signaling compared to control tissue. Together, these data suggest that NF-κB may contribute to fibrotic tendon healing through both inflammation-dependent and inflammation-independent functions, such as NF-κB–mediated cell survival.
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影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
DOI：
10.2147/ccid.s50046
发表时间：
2014
期刊：
Clinical, cosmetic and investigational dermatology
影响因子：
--
作者：
Darby IA;Laverdet B;Bonté F;Desmoulière A
通讯作者：
Desmoulière A
影响因子：
3
作者：
Baum J;Duffy HS
通讯作者：
Duffy HS
影响因子：
4.8
作者：
Best, Katherine T.;Loiselle, Alayna E.
通讯作者：
Loiselle, Alayna E.
影响因子：
1.1
作者：
Gao, Lin Lin;Chang, James
通讯作者：
Chang, James