Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice
Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice
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DOI：
10.1152/ajplung.90594.2008
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发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Ingenito, E. P.
中科院分区：
文献类型：
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作者：
Hoffman, A. M.;Shifren, A.;Ingenito, E. P.
Hoffman AM, Shifren A, Mazan MR, Gruntman AM, Lascola KM, Nolen-Walston RD, Kim CF, Tsai L, Pierce RA, Mecham RP, Ingenito EP。小鼠代偿性肺再生和祖细胞增殖的基质调节。[J] .中国生物医学工程学报，2016,31(4):387 - 398。首次发表于2009年11月13日；doi: 10.1152 / ajplung.90594.2008。-机械应力是肺形态发生、出生后肺发育和代偿性肺再生的重要调节因子。机械应力对干细胞或祖细胞的影响尚不清楚。我们研究了上皮祖细胞的增殖反应，包括双免疫反应性（CCSP和pro - c）祖细胞（CCSP +/SP-C +）和II型肺泡上皮细胞（ATII），是否受到肺气肿肺中发现的物理因素的影响，包括弹性后坐力丧失、弹性蛋白含量降低和肺泡破坏。小鼠接受单肺全肺切除术（PNY）来调节肺压（机械应力）并刺激肺再生。对照组小鼠进行假开胸手术。采用不同程度的压实来部分或完全消除这种机械应力。在弹性蛋白不足的小鼠（弹性蛋白+/-，ELN +/-）和弹性酶治疗的小鼠（弹性酶诱导的肺气肿）中，评估了对经肺压力分级变化的反应。评估CCSP +/SP-C +、Clara细胞和ATII的生理再生、形态测定（线性平均截距；Lmi）和增殖反应。PNY后的通气可显著降低肺压、再生、CCSP +/SP-C +、Clara细胞和ATII的增殖。在ELN +/-组中，CCSP +/SP-C +和ATII增殖反应完全消失，尽管代偿性肺再生没有明显改变。相比之下，在弹性酶损伤小鼠中，代偿性肺再生明显减少，ATII而非CCSP +/SP-C +增殖反应受损。弹性蛋白酶损伤也降低了CCSP +/SP-C +的基线丰度，并且发现CCSP +/SP-C +从细支气管肺泡管交界处移位。这些数据表明，细胞外基质的质量，包括弹性蛋白含量、机械应力和肺泡完整性，强烈影响成年小鼠肺的再生能力和细胞增殖模式。
Hoffman AM, Shifren A, Mazan MR, Gruntman AM, Lascola KM, Nolen-Walston RD, Kim CF, Tsai L, Pierce RA, Mecham RP, Ingenito EP. Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice. Am J Physiol Lung Cell Mol Physiol 298: L158-L168, 2010. First published November 13, 2009; doi: 10.1152/ajplung.90594.2008.-Mechanical stress is an important modulator of lung morphogenesis, postnatal lung development, and compensatory lung regrowth. The effect of mechanical stress on stem or progenitor cells is unclear. We examined whether proliferative responses of epithelial progenitor cells, including dually immunoreactive (CCSP and proSP-C) progenitor cells (CCSP +/SP-C +) and type II alveolar epithelial cells (ATII), are affected by physical factors found in the lung of emphysematics, including loss of elastic recoil, reduced elastin content, and alveolar destruction. Mice underwent single lung pneumonectomy (PNY) to modulate transpulmonary pressure (mechanical stress) and to stimulate lung regeneration. Control mice underwent sham thoracotomy. Plombage of different levels was employed to partially or completely abolish this mechanical stress. Responses to graded changes in transpulmonary pressure were assessed in elastin-insufficient mice (elastin +/-, ELN +/-) and elastase-treated mice with elastase-induced emphysema. Physiological regrowth, morphometry (linear mean intercept; Lmi), and the proliferative responses of CCSP +/SP-C +, Clara cells, and ATII were evaluated. Plombage following PNY significantly reduced transpulmonary pressure, regrowth, and CCSP +/SP-C +, Clara cell, and ATII proliferation following PNY. In the ELN +/- group, CCSP +/SP-C + and ATII proliferation responses were completely abolished, although compensatory lung regrowth was not significantly altered. In contrast, in elastase-injured mice, compensatory lung regrowth was significantly reduced, and ATII but not CCSP +/SP-C + proliferation responses were impaired. Elastase injury also reduced the baseline abundance of CCSP +/SP-C +, and CCSP +/SP-C + were found to be displaced from the bronchioalveolar duct junction. These data suggest that qualities of the extracellular matrix including elastin content, mechanical stress, and alveolar integrity strongly influence the regenerative capacity of the lung, and the patterns of cell proliferation in the lungs of adult mice.