Integrins beta1, alpha6, and alpha3 contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms.
Integrins beta1, alpha6, and alpha3 contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms.
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整合素β1、α6和α3通过不同的机制促进机械应变诱导的胎肺II型上皮细胞的分化。
DOI：
10.1152/ajplung.00189.2005
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Ingber,DonaldE
中科院分区：
文献类型：
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作者：
Sanchez-Esteban,Juan;Wang,Yulian;Filardo,EdwardJ;Rubin,LewisP;Ingber,DonaldE
Mechanical forces regulate lung maturation in the fetus by promoting type II epithelial differentiation. However, the cell surface receptors that transduce these mechanical cues into cellular responses remain largely unknown. When distal lung type II epithelial cells isolated from embryonicday 19rat fetuses were cultured on flexible plates coated with laminin, fibronectin, vitronectin, collagen, or elastin and exposed to a level of mechanical strain (5%) similar to that observed in utero, transmembrane signaling responses were induced under all conditions, as measured by ERK activation. However, mechanical stress maximally increased expression of the type II cell differentiation marker surfactant protein C when cells were cultured on laminin substrates. Strain-induced alveolar epithelial differentiation was inhibited by interfering with cell binding to laminin using soluble laminin peptides (IKVIV or YIGSR) or blocking antibodies against integrin β1, α3, or α6. Additional studies were carried out with substrates coated directly with different nonactivating anti-integrin antibodies. Blocking integrin β1and α6binding sites inhibited both cell adhesion and differentiation, whereas inhibition of α3prevented differentiation without altering cell attachment. These data demonstrate that various integrins contribute to mechanical control of type II lung epithelial cell differentiation on laminin substrates. However, they may act via distinct mechanisms, including some that are independent of their cell anchoring role.
