Premium
Novel role of NF‐κB‐dependent miR‐146a induced by diazoxide preconditioning in stem cell survival
Author(s) -
Suzuki Yoko,
Kim Ha Won,
Haider Husnain Kh,
Ashraf Muhammad
Publication year - 2010
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.24.1_supplement.1027.6
Subject(s) - gene knockdown , cytoprotection , stem cell , mesenchymal stem cell , nf κb , microrna , cancer research , microbiology and biotechnology , transplantation , apoptosis , chemistry , biology , signal transduction , medicine , biochemistry , gene
We have previously reported that preconditioning (PC) of bone marrow‐derived mesenchymal stem cells (MSCs) with diazoxide (DZ) improved their survival via NF‐κB signaling. MicroRNAs (miRs) are critical regulators for a wide variety of biological events including apoptosis and differentiation. However, the role of DZ‐induced miRs in stem cell survival remains unknown. Here we show that miR‐146a is the major miR induced by DZ treatment and plays a pivotal role in MSCs survival through NF‐κB signaling. PC of MSCs with DZ (200 μM) for 3 hrs significantly increased phosphorylation of Akt as well as nuclear NF‐κB translocation, thereby improving MSCs survival as evaluated by lactate dehydrogenase (LDH) release assay (45% decrease). Importantly, miR‐146a expression was increased by DZ treatment and knockdown of miR‐146a abolished DZ‐induced cytoprotective effects. In addition, knockdown of NF‐κB ablated DZ‐induced miR‐146a expression as well as MSCs survival, indicating miR‐146a is a downstream of NF‐κB and plays a key role in stem cell survival. We are in the process of determining the target genes of miR‐146a by using PCR array as well as computational analysis. Together, these data demonstrated that cytoprotection afforded by PC with DZ was regulated by miR‐146a which may be a novel therapeutic target for stem cell transplantation therapy. Grant supports: NIH R37 HL074272 , HL080686 , HL087246 , HL087288 , HL089535