Laminin α5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through β1 integrin signaling
Laminin α5 is necessary for submandibular gland epithelial morphogenesis and influences FGFR expression through β1 integrin signaling
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DOI：
10.1016/j.ydbio.2007.04.031
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发表时间：
2007-08-01
影响因子：
2.7
通讯作者：
Hoffman, Matthew P.
中科院分区：
文献类型：
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作者：
Rebustini, Ivan T.;Patel, Vaishali N.;Hoffman, Matthew P.
层粘连蛋白α链在发育过程中具有独特的时空表达模式，并且确定其功能对于理解上皮细胞形态发生的调节是必要的。我们研究了层粘连蛋白α 5在小鼠下颌下腺（SMGs）中的功能。Lama 5（-/-）SMG具有显著的表型：上皮细胞分裂延迟，但发生增殖; FGFR 1b和FGFR 2b减少，但Lamal表达无差异;在发育后期，上皮细胞组织和管腔形成被破坏。在野生型SMG中，α 5和油存在于上皮裂缝中，但随着分支开始，α 5表达增加，而α 1降低。Lama 5 siRNA降低分支、p42 MAPK磷酸化和FGFR表达，并且分支被FGF 10拯救。FGFR siRNA降低了Lama 5，表明FGFR信号传导为Lama 5表达提供了正反馈。抗β 1整联蛋白抗体降低FGFR和Lama 5表达，表明β 1整联蛋白信号传导为Lama 5和FGFR表达提供正反馈。有趣的是，1 tga 3（-/-）：Itga 6（-/-）SMG具有与Lania 5（-/-）相似的表型。我们的研究结果表明，层粘连蛋白α 5控制SMG上皮形态发生通过I整合素信号通过调节FGFR的表达，这也间接调节Lama 5的表达。这些数据将分支形态发生期间基底膜组成的变化与FGFR表达和信号传导联系起来。(c)2007年爱思唯尔公司All rights reserved.
Laminin alpha chains have unique spatiotemporal expression patterns during development and defining their function is necessary to understand the regulation of epithelia] morphogenesis. We investigated the function of laminin alpha 5 in mouse submandibular glands (SMGs). Lama5(-/-) SMGs have a striking phenotype: epithelial clefting is delayed, although proliferation occurs; there is decreased FGFR1b and FGFR2b, but no difference in Lamal expression; later in development, epithelial cell organization and lumen formation are disrupted. In wild-type SMGs alpha 5 and oil are present in epithelial clefts but as branching begins a5 expression increases while alpha l decreases. Lama5 siRNA decreased branching, p42 MAPK phosphorylation, and FGFR expression, and branching was rescued by FGF10. FGFR siRNA decreased Lama5 suggesting that FGFR signaling provides positive feedback for Lama5 expression. Anti-beta 1 integrin antibodies decreased FGFR and Lama5 expression, suggesting that [ I integrin signaling provides positive feedback for Lama5 and FGFR expression. Interestingly, the 1tga3(-/-) :Itga6(-/-) SMGs have a similar phenotype to Lania5(-/-). Our findings suggest that laminin alpha 5 controls SMG epithelial morphogenesis through I integrin signaling by regulating FGFR expression, which also reciprocally regulates the expression of Lama5. These data link changes in basement membrane composition during branching morphogenesis with FGFR expression and signaling. (c) 2007 Elsevier Inc. All rights reserved.