MicroRNA-145 regulates the differentiation of human adipose-derived stem cells to smooth muscle cells via targeting Krüppel-like factor 4

Abstract

Understanding the molecular mechanisms underlying human adipose-derived stem cell (hASC) differentiation to smooth muscle may contribute to the development of effective therapies for relevant muscle defects, such as bladder wall and urethral defects. A previous study described the differentiation of hASCs to smooth muscle cells (SMCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-4 (BMP4) treatment. The present study investigated whether microRNA-145 (miR-145) may be involved in the process of hASC differentiation. The expression of miR-145 was significantly increased during differentiation of ASCs to SMCs. SMC-specific genes and proteins, including a-smooth muscle actin (α-SMA), smooth muscle protein-22α(SM22α), calponin and myosin heavy chain (SM-MHC) were upregulated by transfection of a miR-145 mimic. By contrast, these factors were downregulated following introduction of antisense oligonucleotides. In addition, Krüppel-like factor 4 (KLF4) levels, which decreased during the differentiation of hASCs, were downregulated when the cells were transfected miR-145 mimics. Futhermore, inhibition of KLF4 by treatment with short-interfering-RNA against KLF4, resulted in increased expression of SMC-specific genes and proteins. In conclusion, the results of the present study demonstrated that by regulating KLF4, miR-145 may be involved in regulating smooth muscle differentiation of ASCs induced by TGF-β1 and BMP4.