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MicroRNA‐301a Alters Dicer Expression in Primary Human Atrial Cells and Bone Marrow‐Derived Mesenchymal Progenitor Cells: Implications for Cardiac Fibrosis
Author(s) -
Muller Alison,
Freed Darren
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb626
Subject(s) - dicer , microrna , phenotype , myofibroblast , progenitor cell , cardiac fibrosis , biology , microbiology and biotechnology , fibrosis , mesenchymal stem cell , cell type , cell , bone marrow , transfection , pathology , small interfering rna , medicine , immunology , stem cell , cell culture , gene , genetics
It is known that multiple cell types can contribute to cardiac fibrosis including both atrial fibroblasts (AFs) and bone marrow‐derived progenitor cells (MPCs). We have previously shown that MPCs display a myofibroblast phenotype in vitro that is linked to altered microRNA(miR)‐301 expression, a miR affiliated with maintaining proliferation in many cell types. We have also shown that miR‐301a influences a dichotomous phenotype in MPCs isolated from patients undergoing open heart surgery. The objective of this experiment was to further understand how this phenotype change may be influenced. We performed a microarray analysis investigating potential targets of miR‐301a. From this screen, Dicer was identified as a potential target of mir‐301a. Dicer is responsible for activating miRs in the cell, therefore altering protein expression and ultimately influencing phenotype. As both MPCs and AFs display a dichotomous phenotype where each cell type displays a phenotype that pathologically contributes to fibrosis, we transfected both MPCs and AFs with miR‐301a. AFs were also isolated from patients undergoing open heart surgery. We performed qRT‐PCR analysis and found that the mRNA of Dicer was significantly reduced in transfected cells, and observed decreases in levels of both mRNA and protein of collagen I and non‐muscle myosin IIA (NMMIIA). These proteins are present in myofibroblasts, the cell type predominantly responsible for causing cardiac fibrosis. Our results provide insight into a possible cellular mechanism that governs the pro‐fibrotic phenotypes of AFs and MPCs, which could be partially caused by altered Dicer expression with its attendant effect on miRNA processing in the cell.