Repair and regeneration of tracheal surface epithelium and submucosal glands in a mouse model of hypoxic-ischemic injury.

Repair and regeneration of tracheal surface epithelium and submucosal glands in a mouse model of hypoxic-ischemic injury.
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DOI:
10.1111/j.1440-1843.2012.02204.x
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发表时间:
2012-10
期刊:
Respirology (Carlton, Vic.)
影响因子:
--
通讯作者:
Gomperts BN
Gomperts BN
中科院分区:
其他
文献类型:
--
作者:
Hegab AE;Nickerson DW;Ha VL;Darmawan DO;Gomperts BN

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异位同体气管移植小鼠模型是一种急性缺氧缺血性损伤的完全修复和再生模型。我们假设,表面上皮和粘膜下腺的修复和再生过程将以一种可复制的模式发生,随后可能是上皮细胞类型的特定标记物的表达。我们使用同基因异位气管移植模型,通过在移植后1、3、5、7、10和14天检测气管移植物,建立细胞修复和再生的时空图谱。我们使用脉冲BrdU和免疫荧光染色来识别和跟踪增殖和修复细胞群。我们在模型中证实了损伤和修复的可重复性,我们发现气管表面上皮和粘膜下腺的各种干/祖细胞和分化细胞群的重现顺序明显。在初始阶段,在损伤后存活的基底细胞和导管细胞增殖,表达K5和K14的细胞重新上皮基底膜。然后这些细胞进一步增殖分化,恢复上皮功能。在这个修复过程中,TROP-2标记了所有修复的粘膜下腺小管和导管。未表达ccsp的浆液细胞早于Clara细胞、粘液细胞和纤毛细胞分化4 ~ 5天。提高我们对气道上皮修复过程的理解将使我们能够识别细胞特异性修复机制,这可以作为导致气道疾病的异常修复的新治疗方法。
The heterotopic syngeneic tracheal transplant mouse model is an acute hypoxic-ischemic injury model that undergoes complete repair and regeneration. We hypothesized that the repair and regeneration process of the surface epithelium and submucosal glands would occur in a reproducible pattern that could be followed by the expression of specific markers of epithelial cell types. We used the syngeneic heterotopic tracheal transplant model to develop a temporal and spatial map of cellular repair and regeneration by examining the tracheal grafts at post-transplant days 1, 3, 5, 7, 10 and 14. We used pulsed BrdU and immunofluorescent staining to identify and follow proliferating and repairing cell populations. We confirmed the reproducibility of the injury and repair in the model and we found a distinct sequence of reappearance of the various stem/ progenitor and differentiated cell populations of the tracheal surface epithelium and submucosal glands. In the initial phase, the basal and duct cells that survived the injury proliferated to re-epithelialize the basement membrane with K5 and K14 expressing cells. Then these cells proliferated further and differentiated to restore the function of the epithelium. During this repair process, TROP-2 marked all repairing submucosal gland tubules and ducts. Non-CCSP-expressing serous cells were found to differentiate 4–5 days before Clara, mucus and ciliated cells. Improving our understanding of the reparative process of the airway epithelium will allow us to identify cell-specific mechanisms of repair that could be used as novel therapeutic approaches for abnormal repair leading to airway diseases.
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