MicroRNA Let-7d Mediated Mesenchymal Stem Cell Exosomes Against Idiopathic Pulmonary Fibrosis Through Epithelial-Mesenchymal Transition Progress

Author:

Liu Jing1,Han Xiudi2,Gu Minghao3,Zhao Qikai3,Li Qian3,Liu Xuedong1

Affiliation:

1. Qingdao University

2. Qingdao Municipal Hospital

3. Medical Department of Qingdao University

Abstract

Abstract

Background Mesenchymal stem cells (MSCs) commonly affect idiopathic pulmonary fibrosis (IPF) through the epithelial-mesenchymal transition (EMT) process. And exosomes of MSCs as a safe cell-free therapy are gradually being emphasized in treating IPF. Meanwhile, miRNA Let-7d expression was reduced in the fibrous formation progression. However, whether miRNA Let-7d regulates the EMT process in IPF through MSC exosomes still requires studies. Methods We extracted MSCs from umbilical cords of female pregnant SD rats. After being cultured and identified, they were transfected with miRNA Let-7d mimics or inhibitors. we collected exosomes from the supernatant that were subsequently injected into the IPF modelled BALB/c mice. IPF and EMT indicators were detected by HE staining, immunohistochemistry, masson staining, western blot and ELISA. Results What we found was that miRNA Let-7d promoted the secretion of exosomes by MSCs. And these exosomes could up-regulate the protein expression of E-Cadherin and down-regulate the protein expression of Fibronectin, COL1A1, COL3A1, N-Cadherin, Slug, and Snail in the EMT pathway in mice lung to reduce the fibrous and collagenous deposition that to alleviate the IPF in the lung. Conclusions In this paper, we investigated the mechanism that miRNA Let-7d up-regulated MSC exosomes against IPF in the EMT process.

Publisher

Research Square Platform LLC

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