Vitronectin is present in epithelial cells of the intact lens andpromotes epithelial mesenchymal transition in lens epithelial explants

[摘要] Purpose: Extracellular matrix (ECM) accumulates during thedevelopment of posterior capsule opacification (PCO). Vitronectin, anECM component that is generally prominent in wound healing, has beendetected in PCO specimens. Here we set out to investigate thedistribution of vitronectin in the lens and determine how it, and otherECM components, influence the lens epithelial phenotype.Methods: Rat lens epithelial explants were cultured on vitronectin,fibronectin, and laminin substrata. Explants were monitored for cellmigration and the appearance of markers for epithelial mesenchymaltransition (EMT), using phase contrast microscopy andimmunohistochemistry, respectively. Explants were also monitored forevidence of Smad signaling. Vitronectin expression was analyzed inembryonic and postnatal rodent lens development by immunohistochemistry,western blotting, and in situ hybridization.Results: Vitronectin, like fibronectin and laminin, provided a goodsubstratum for cellular attachment and migration. However, in the caseof vitronectin and fibronectin, this was accompanied by a majorphenotypic change. On either vitronectin or fibronectin, but notlaminin, most of the cells became elongated, spindle-shaped and werestrongly reactive for filamentous α-smooth muscle actin. In theserespects this transition was typical of the well known TGFβ-inducedEMT. In explants cultured on vitronectin and fibronectin, but notlaminin, cell nuclei showed prominent reactivity for Smad 2/3.Vitronectin was also shown to be expressed during embryonic andpostnatal development. Initially mRNA and protein were detected in alllens cells, however as development progressed, expression becamerestricted to cells of the epithelium and transition zone.Conclusions: The results clearly show that lens cell engagement witha vitronectin or a fibronectin, but not laminin, substratum has a potentEMT promoting effect and that Smad 2/3 signaling is involved. Thus whenconsidering strategies to slow or prevent PCO, these results highlightthe need to take into account ECM molecules such as vitronectin thathave the capacity to promote EMT.

[学科分类] 生物化学/生物物理