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A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers

机译:急性肺损伤的小鼠模型鉴定了促进组织修复及其生物标志物的生长因素

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Type II alveolar epithelial cells (AEC2s) play a crucial role in the regeneration of type I AECs after acute lung injury. The mechanisms underlying the regeneration of AEC2s are not fully understood. To address this issue, here, we investigated a murine model of acute lung injury using mice expressing human Diphtheria Toxin Receptor (DTR) under the control of Lysozyme M promoter (LysM-DTR). DT injection induced the depletion of AEC2s, alveolar macrophages, and bone marrow (BM)-derived myeloid cells in LysM-DTR mice, and the mice died within 6 days after DT injection. Apoptotic AEC2s and bronchiolar epithelial cells appeared at 24 hr, whereas Ki67-positive proliferating cells appeared in the alveoli and bronchioles in the lung of LysM-DTR mice at 72-96 hr after DT injection. Transfer of wild-type BM cells into LysM-DTR mice accelerated the regeneration of AEC2s along with the up-regulation of several growth factors. Moreover, several metabolites were significantly decreased in the sera of LysM-DTR mice compared with WT mice after DT injection, suggesting that these metabolites might be biomarkers to predict AEC2s injury. Together, LysM-DTR mice might be useful to identify growth factors to promote lung repair and the metabolites to predict the severity of lung injury.
机译:II型肺泡上皮细胞(AEC2S)在急性肺损伤后I型AECs的再生中起至关重要的作用。依据AEC2S的再生的机制尚不完全明白。为了解决这个问题,在这里,我们研究了在溶菌酶M启动子(Lysm-DTR)的控制下使用表达人白喉毒素受体(DTR)的小鼠的急性肺损伤的鼠模型。 DT注射诱导在Lysm-DTR小鼠中耗尽AEC2​​S,肺泡巨噬细胞和骨髓(BM)的骨髓细胞,小鼠在DT注射后6天内死亡。凋亡AEC2S和支气管上皮细胞出现在24小时,而DT注射后72-96小时的Lysm-DTR小鼠的肺泡和支气管中出现Ki67阳性增殖细胞。将野生型BM细胞转移到LYSM-DTR小鼠中加速了AEC2S的再生以及几种生长因子的上调。此外,在DT注射后与WT小鼠相比,在Lysm-DTR小鼠的血清中,几个代谢物显着降低,表明这些代谢物可能是预测AEC2S损伤的生物标志物。 Lysm-DTR小鼠在一起可能有助于鉴定促进肺部修复和代谢物预测肺损伤的严重程度的生长因子。

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