Mfge8 is critical for mammary gland remodeling during involution
Mfge8 is critical for mammary gland remodeling during involution
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DOI：
10.1091/mbc.e05-02-0128
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Sheppard, D
中科院分区：
文献类型：
--
作者：
Atabai, K;Fernandez, R;Sheppard, D
细胞凋亡是正常乳腺发育的关键过程，凋亡细胞的快速清除可防止与死亡细胞释放细胞内抗原相关的组织损伤。乳脂球-EGF-因子8（Mfge 8）是一种在乳腺上皮中大量表达的乳糖蛋白，并且已显示促进脾巨噬细胞对凋亡淋巴细胞的清除。我们报告说，破坏Mfge 8的小鼠有正常的乳腺发育，直到退化。然而，异常乳腺重塑观察哺乳后Mfge 8突变小鼠。在退化早期，Mfge 8突变小鼠乳腺内凋亡细胞数量增加，与肺泡萎陷和脂肪细胞再增殖延迟相关。随着退化的进展，Mfge 8突变体发生炎症，如通过乳腺组织切片的CD 45和CD 11b染色所评估的。随着怀孕次数的增加，Mfge 8突变小鼠的乳腺导管网络出现进行性扩张。这些数据表明，Mfge 8调节乳腺退化期间凋亡上皮细胞的清除，并且Mfge 8的缺乏导致炎症和异常乳腺重塑。
Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with the release of intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to facilitate the clearance of apoptotic lymphocytes by splenic macrophages. We report that mice with disruption of Mfge8 had normal mammary gland development until involution. However, abnormal mammary gland remodeling was observed postlactation in Mfge8 mutant mice. During early involution, Mfge8 mutant mice had increased numbers of apoptotic cells within the mammary gland associated with a delay in alveolar collapse and fat cell repopulation. As involution progressed, Mfge8 mutants developed inflammation as assessed by CD45 and CD11b staining of mammary gland tissue sections. With additional pregnancies, Mfge8 mutant mice developed progressive dilatation of the mammary gland ductal network. These data demonstrate that Mfge8 regulates the clearance of apoptotic epithelial cells during mammary gland involution and that the absence of Mfge8 leads to inflammation and abnormal mammary gland remodeling.