title: Functional expression of smooth muscle-specific ion channels in TGF-β(1)-treated human adipose-derived mesenchymal stem cells.
abstract: Human adipose tissue-derived mesenchymal stem cells (hASCs) have the power to differentiate into various cell types including chondrocytes, osteocytes, adipocytes, neurons, cardiomyocytes, and smooth muscle cells. We characterized the functional expression of ion channels after transforming growth factor-β1 (TGF-β1)-induced differentiation of hASCs, providing insights into the differentiation of vascular smooth muscle cells. The treatment of hASCs with TGF-β1 dramatically increased the contraction of a collagen-gel lattice and the expression levels of specific genes for smooth muscle including α-smooth muscle actin, calponin, smooth mucle-myosin heavy chain, smoothelin-B, myocardin, and h-caldesmon. We observed Ca(2+), big-conductance Ca(2+)-activated K(+) (BKCa), and voltage-dependent K(+) (Kv) currents in TGF-β1-induced, differentiated hASCs and not in undifferentiated hASCs. The currents share the characteristics of vascular smooth muscle cells (SMCs). RT-PCR and Western blotting revealed that the L-type (Cav1.2) and T-type (Cav3.1, 3.2, and 3.3), known to be expressed in vascular SMCs, dramatically increased along with the Cavβ1 and Cavβ3 subtypes in TGF-β1-induced, differentiated hASCs. Although the expression-level changes of the β-subtype BKCa channels varied, the major α-subtype BKCa channel (KCa1.1) clearly increased in the TGF-β1-induced, differentiated hASCs. Most of the Kv subtypes, also known to be expressed in vascular SMCs, dramatically increased in the TGF-β1-induced, differentiated hASCs. Our results suggest that TGF-β1 induces the increased expression of vascular SMC-like ion channels and the differentiation of hASCs into contractile vascular SMCs.
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Eun Su
authors.initials: ES
authors.lastname: Jeon
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Hong
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006614:Hindlimb; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D018919:Neovascularization, Physiologic; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function; D012039:Regional Blood Flow; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: TGF-β1; human adipose tissue-derived mesenchymal stem cells; ion channel; vascular smooth muscle