title: miR-18b inhibits TGF-β1-induced differentiation of hair follicle stem cells into smooth muscle cells by targeting SMAD2.
abstract: Human hair follicle mesenchymal stem cells (hHF-MSCs) are capable of differentiating into smooth muscle cells (SMCs) in response to transforming growth factor-β (TGF-β), and thus can be used for cardiovascular tissue engineering and regenerative medicine. However, the precise molecular mechanisms underlying SMC conversion of hHF-MSCs are still undefined. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression post-transcriptionally by binding to the complementary sequences of targeted mRNAs. Accumulating evidence indicates that miRNAs are associated with SMC differentiation in vitro andin vivo. In this study, we revealed that miR-18b was significantly downregulated during TGF-β1-induced hHF-MSCs differentiation into SMC using miRNA array profiling and quantitative RT- PCR (qRT-PCR). Over-expression of miR-18b in hHF-MSCs led to remarkable downregulation of SMC-specific markers such as SMA and calponin proteins. On the contrary, inhibition of endogenous miR-18b by its antisense oligonucleotide antagomir-18b reversed the changes of SMA and calponin proteins. We also showed that SMAD2, a key transcription regulator in TGF-β signaling which was involved in SMC differentiation, is regulated by miR-18b. miR-18b could suppress the expression of SMAD2 protein by targeting the 3'UTR of SMAD2 gene without affecting its mRNA level in hHF-MSCs. Moreover, knockdown of SMAD2 by RNA interference could block the effect of inhibition of miR-18b on SMC differentiation, indicating that SMAD2 contributed to miR-18b mediated regulation of TGF-β-induced SMC differentiation. In conclusion, this study demonstrated that miR-18b regulated the TGF-β1-induced differentiation of hHF-MSCs into SMCs by targeting SMAD2 gene, and provided novel insights into the regulatory mechanisms of TGF-β-induced SMC differentiation.
authors.affiliation: Department of Pathobiology, The Key Lab of Educational Ministry, College of Basic Medical Sciences, Jilin University, China; Department of Pathology, Fist Hospital of Jilin University, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Jinyu
authors.initials: J
authors.lastname: Liu
authors.forename: Shichao
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Bai
authors.forename: Tingting
authors.initials: T
authors.lastname: Bai
authors.forename: Yimei
authors.initials: Y
authors.lastname: Wang
authors.forename: Meiying
authors.initials: M
authors.lastname: Li
authors.forename: Yaolin
authors.initials: Y
authors.lastname: Song
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051899:Smad2 Protein / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C522576:MIRN18A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta
keywords: Differentiation; MicroRNA; SMAD2; Smooth muscle cell; TGF-β