title: Selective expression of TSPAN2 in vascular smooth muscle is independently regulated by TGF-β1/SMAD and myocardin/serum response factor.
abstract: Tetraspanins (TSPANs) comprise a large family of 4-transmembrane domain proteins. The importance of TSPANs in vascular smooth muscle cells (VSMCs) is unexplored. Given that TGF-β1 and myocardin (MYOCD) are potent activators for VSMC differentiation, we screened for TGF-β1 and MYOCD/serum response factor (SRF)-regulatedTSPANsin VSMC by using RNA-seq analyses and RNA-arrays.TSPAN2was found to be the onlyTSPANfamily gene induced by TGF-β1 and MYOCD, and reduced by SRF deficiency in VSMCs. We also found thatTSPAN2is highly expressed in smooth muscle-enriched tissues and down-regulated inin vitromodels of VSMC phenotypic modulation.TSPAN2expression is attenuated in mouse carotid arteries after ligation injury and in failed human arteriovenous fistula samples after occlusion by dedifferentiated neointimal VSMC.In vitrofunctional studies showed that TSPAN2 suppresses VSMC proliferation and migration. Luciferase reporter and chromatin immunoprecipitation assays demonstrated thatTSPAN2is regulated by 2 parallel pathways, MYOCD/SRF and TGF-β1/SMAD,viadistinct binding elements within the proximal promoter. Thus, we identified the first VSMC-enriched and MYOCD/SRF and TGF-β1/SMAD-dependentTSPANfamily member, whose expression is intimately associated with VSMC differentiation and negatively correlated with vascular disease. Our results suggest thatTSPAN2may play important roles in vascular disease.-Zhao, J., Wu, W., Zhang, W., Lu, Y. W., Tou, E., Ye, J., Gao, P., Jourd'heuil, D., Singer, H. A., Wu, M., Long, X. Selective expression of TSPAN2 in vascular smooth muscle is independently regulated by TGF-β1/SMAD and myocardin/serum response factor.
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Yao Wei
authors.initials: YW
authors.lastname: Lu
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Emiley
authors.initials: E
authors.lastname: Tou
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Jiemei
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jourd'heuil
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Singer
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA.
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA longx@mail.amc.edu.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Long
mesh_terms: D002454:Cell Differentiation; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D051785:Smad Proteins; D059470:Tetraspanins; D015534:Trans-Activators; D053773:Transforming Growth Factor beta1; D000099251:Myocardin; C512650:TSPAN2 protein, human; C512651:Tspan2 protein, mouse
keywords: arteriovenous fistula; differentiation; phenotypic modulation; tetraspanins