Premium
MicroRNA miR‐145 Modulates p38 MAP Kinase Pathway in Cardiac Fibroblasts to Suppress Cardiac Fibrosis
Author(s) -
Marosis Sam,
Sawant Dwitiya,
McCallinhart Patricia,
Trask Aaron,
Thomas Shelby,
Lilly Brenda
Publication year - 2019
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.2019.33.1_supplement.644.2
Subject(s) - cardiac fibrosis , microrna , fibrosis , signal transduction , kinase , myocardial fibrosis , cancer research , mitogen activated protein kinase , microbiology and biotechnology , biology , transforming growth factor , p38 mitogen activated protein kinases , protein kinase a , medicine , gene , biochemistry
Cardiac fibrosis is associated with many types of cardiovascular diseases and is characterized by the deposition of excess extracellular matrix by the cardiac fibroblasts. Previous studies demonstrated that microRNA miR‐145 acts as an inhibitor of fibrosis by targeting the profibrotic TGFβ pathway. Our preliminary data suggest that within the TGFβ pathway, miR‐145 specifically targets the p38 mitogen‐activated protein (MAP) kinase signaling, which is known to activate cardiac fibroblasts and drive the fibrotic response. Therefore, I hypothesize that miR‐145 targets the p38 MAP kinase pathway to regulate cardiac fibroblast activation and suppress fibrosis. Human cardiac fibroblasts (hCFs) were transfected with a miR‐145 mimic or a control mimic and TGFβ, a fibrotic agonist, was added to activate fibroblasts. Cells were processed for RNA and quantitative‐PCR was used to measure relative expression of genes within the p38 MAP kinase pathway. My findings show that MAP2K3 and MAP4K4 expression are inhibited by miR‐145 in activated hCFs. Further, TGFβ 3 and RGS2, both negative regulators of fibrosis, were induced in miR‐145 treated cells. These data indicate that miR‐145 modulates components of the p38 MAP kinase signaling pathway, which may contribute to its ability to regulate cardiac fibrosis. Ongoing studies will examine if overexpression of miR‐145 in a mouse model will affect the expression of these p38 MAP kinase mediators and contribute to a reduction in cardiac fibrosis. Support or Funding Information This project was supported by the American Physiological Society‐Undergraduate Research Excellency Fellowship, the American Heart Association Summer Undergraduate Research Fellowship, and the National Institute of Health grant R01‐HL‐135657 (to B. Lilly). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .