Low let-7d exosomes from pulmonary vascular endothelial cells drive lung pericyte fibrosis through the TGF βRI/FoxM1/Smad/β-catenin pathway.

Low let-7d exosomes from pulmonary vascular endothelial cells drive lung pericyte fibrosis through the TGFβRI/FoxM1/Smad/β-catenin pathway. J Cell Mol Med. 2020 Nov 12;: Authors: Xie H, Gao YM, Zhang YC, Jia MW, Peng F, Meng QH, Wang YC Abstract The pathogenesis of pulmonary fibrosis (PF) was mediated by the progressive deposition of excessive extracellular matrix, but little is known about the regulatory mechanisms of fibrogenesis by lung pericytes. The mouse PF model was established by treatment with bleomycin, followed by isolation of exosomes from mouse broncho-alveolar lavage fluids by the centrifuge method. Relative mRNA/microRNA levels and protein expression were assessed by qRT-PCR and Western blotting, respectively. The binding of let-7d with gene promoter was validated by dual-luciferase reporter assay. Protein interactions were verified via GST pull-down and co-immunoprecipitation. Nuclear retention of Smad3 was analysed by extraction of cytoplasmic and nuclear fraction of pericytes followed by Western blotting. Association of FoxM1 with gene promoter was detected by EMSA and ChIP-PCR methods. FoxM1 expression is significantly elevated in human lung fibroblasts of PF patients and mouse PF model. The expression of let-7d is repressed in exosomes derived from broncho-alveolar lavage fluids of PF mice. Let-7d or FoxM1 knockdown suppressed the expression of FoxM1, Smad3, β-catenin, Col1A and α-SMA expression in mouse lung ...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research