Aji Kaisaier, Zhang Yun, Aimaiti Abudusaimi, Wang Yujie, Rexiati Mulati, Azhati Baihetiya, Tusong Hamulati, Cui Lei, Wang Chen
Department of Urology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
Department of Orthopedics, Tongji University School of Medicine, Shanghai 200092, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3787-3795. doi: 10.3892/mmr.2017.6478. Epub 2017 Apr 13.
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.
了解人类脂肪来源干细胞（hASC）向平滑肌分化的分子机制，可能有助于开发针对相关肌肉缺陷（如膀胱壁和尿道缺陷）的有效治疗方法。先前的一项研究描述了通过转化生长因子-β1（TGF-β1）和骨形态发生蛋白-4（BMP4）处理将hASC分化为平滑肌细胞（SMC）。本研究调查了微小RNA-145（miR-145）是否可能参与hASC分化过程。在ASC向SMC分化过程中，miR-145的表达显著增加。通过转染miR-145模拟物，SMC特异性基因和蛋白质，包括α-平滑肌肌动蛋白（α-SMA）、平滑肌蛋白-22α（SM22α）、钙调蛋白和肌球蛋白重链（SM-MHC）被上调。相比之下，引入反义寡核苷酸后，这些因子被下调。此外，在hASC分化过程中水平降低的Krüppel样因子4（KLF4），在细胞转染miR-145模拟物时被下调。此外，用针对KLF4的短干扰RNA处理抑制KLF4，导致SMC特异性基因和蛋白质的表达增加。总之，本研究结果表明，通过调节KLF4，miR-145可能参与调节TGF-β1和BMP4诱导的ASC平滑肌分化。
