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PPAR Gamma-Regulated MicroRNA 199a-5p Underlies Bone Marrow Adiposity in Aplastic Anemia.

Abstract：

:Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation has been implicated in the fatty bone marrow and defective hematopoiesis of aplastic anemia (AA). However, the underlying molecular mechanism remains to be investigated. In this study, we found that microRNA 199a-5p (miR-199a-5p) exhibits significantly higher expression in AA BM-MSCs compared with the normal control and is demonstrated to facilitate adipogenic differentiation of BM-MSCs through lentivirus-mediated miR-199a overexpression. Mechanistic investigation reveals that miR-199a-5p could be regulated by PPAR gamma (PPARγ) in a transcription-independent manner and regulates adipogenic differentiation by targeting the expression of transforming growth factor beta induced (TGFBI), which is subsequently validated as a negative regulator of adipogenesis. Besides, the positive correlation between PPARγ and miR-199a-5p expression as well as the inverse relationship between miR-199a-5p and TGFBI expression in normal and AA BM-MSCs was observed. Altogether, our work demonstrates that PPARγ-regulated miR-199a-5p promotes adipogenesis of BM-MSCs by inhibiting TGFBI expression, which might be a novel mechanism underlying the bone marrow adiposity in AA, and provides promising therapeutic targets for AA treatment.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Zhang X,Liu L,Dou C,Cheng P,Liu L,Liu H,Ren S,Wang C,Jia S,Chen L,Zhang H,Chen M

doi

10.1016/j.omtn.2019.07.005

subject

Has Abstract

pub_date

2019-09-06 00:00:00

pages

678-687

issn

2162-2531

pii

S2162-2531(19)30195-7

journal_volume

17

pub_type

杂志文章

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