Open AccessLats1/2-Mediated Alteration of Hippo Signaling Pathway Regulates the Fate of Bone Marrow-Derived Mesenchymal Stem Cells
Author(s) -
Lang Li,
Dong Liu,
Yifeng Wang,
Xiuhong Zhang,
Jie Yan
Publication year - 2018
Publication title -
biomed research international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 126
eISSN - 2314-6141
pISSN - 2314-6133
DOI - 10.1155/2018/4387932
Subject(s) - hippo signaling pathway , microbiology and biotechnology , mesenchymal stem cell , runx2 , cancer research , biology , signal transduction , stem cell , transcription factor , biochemistry , gene
Bone marrow-derived mesenchymal stem cells (BMSCs) can be used to enhance lung repair in acute respiratory distress syndrome (ARDS); however, the repairing effect is limited by poor homing and retention of BMSCs. The purpose of this study was to investigate whether Lats1 and Lats2 -mediated alteration of Hippo signaling pathway could promote the differentiation, proliferation, and migration of BMSCs. BMSCs were transduced by lentiviral vectors for high and low expression of Lats1 and Lats2 . The expression levels of Lats1 , Lats2 , YAP, and 14-3-3, respectively, were assessed to clarify the regulatory effects of Lats1 and Lats2 on Hippo signaling. Osteogenic (Runx2 and OSX) and adipogenic (C/EBP α and PPAR- γ ) transcription factors were determined to clarify the effects of Hippo signaling on BMSCs differentiation. The effects of Hippo signaling on BMSCs proliferation and horizontal and vertical migration were also measured by CCK-8, scratch assay, and Transwell migration assay, respectively. Lentiviral transduction efficiency could reach 93.11%–97.14%. High and low expression of Lats1 and Lats2 could activate and inhibit the Hippo signaling pathway, respectively. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs differentiation into osteoblasts and adipocytes. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs proliferation and horizontal and vertical migration, respectively. Our studies suggest that Lats1 / 2 -meidiated inhibition of Hippo signaling in BMSCs may optimize their effects of tissue repair in ARDS, suggesting a novel strategy for enhancing disease therapeutics.