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let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts

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AJP Lung Cellular and Molecular Physiology

Published online on

Abstract

MicroRNAs (microRNAs) are small non-coding RNAs that inhibit protein expression. We have previously shown that the inhibition of the microRNA let-7d in epithelial cells caused changes consistent with Epithelial to Mesenchymal Transition (EMT) both in vitro and in vivo. The aim of this study was to determine whether introduction of let-7d into fibroblasts will alter their mesenchymal properties. Transfection of primary fibroblasts with let-7d caused a decrease in expression of the mesenchymal markers αSMA, N-Cadherin and FSP-1, as well as an increase in the epithelial marker TJP-1. Phenotypic changes were also present, including a delay in wound healing, reduced motility, and proliferation of fibroblasts following transfection. In addition, we examined the effects of transfection on fibroblast responsiveness to TGFβ, an important factor in many fibrotic processes such as lung fibrosis, and found that let-7d transfection significantly attenuated HMGA2 level induction by TGFβ. Our results indicate administration of the epithelial microRNA let-7d can significantly alter the phenotype of primary fibroblasts.