Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation.
Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation.
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DOI：
10.1186/1465-9921-13-1
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发表时间：
2012-01-03
影响因子：
5.8
通讯作者：
Schwarz MA
中科院分区：
文献类型：
--
作者：
Chen Y;Legan SK;Mahan A;Thornton J;Xu H;Schwarz MA
远端肺泡形态发生的标志是肺泡型(AT)-II向AT- i细胞分化，形成主要的气体交换部位，即肺泡/血管界面。内皮单核细胞激活多肽（EMAP） II是一种具有抗血管生成特性的内源性蛋白，在肺形态发生过程中严重破坏远端肺新生血管和肺泡形成，并在支气管肺发育不良婴儿的发育不良肺泡区大量表达。EMAP II是否对ATII→ATI反分化有直接或间接的影响尚未被探讨。在受控的非血管环境中，利用ATII→ATI细胞反分化的体外模型来证明一种血管介质对远端上皮细胞分化的贡献。本研究表明，EMAP II通过增加细胞凋亡和抑制ATI标记物的表达，显著阻断了ATII→ATI细胞的转分化。此外，EMAP ii处理的ATII细胞表现出肌成纤维细胞特征，包括细胞增殖升高，肌动蛋白细胞骨架应激纤维和Rho-GTPase活性增加，核细胞质体积增加。然而，EMAP ii处理的细胞不表达肌成纤维细胞标记物desmin或αSMA。我们的研究结果表明，EMAP II干扰ATII→ATI转分化，导致非肌成纤维细胞增殖。这些数据表明转分化肺泡细胞可能是EMAP II诱导肺泡发育不良的靶点。
Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia.
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影响因子：
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影响因子：
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作者：
Pozharskaya V;Torres-González E;Rojas M;Gal A;Amin M;Dollard S;Roman J;Stecenko AA;Mora AL
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