PMID- 28258189
OWN - NLM
STAT- MEDLINE
DCOM- 20170912
LR  - 20181113
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 31
IP  - 6
DP  - 2017 Jun
TI  - Selective expression of TSPAN2 in vascular smooth muscle is independently 
      regulated by TGF-beta1/SMAD and myocardin/serum response factor.
PG  - 2576-2591
LID - 10.1096/fj.201601021R [doi]
AB  - 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-beta1 and myocardin (MYOCD) are potent activators for VSMC 
      differentiation, we screened for TGF-beta1 and MYOCD/serum response factor 
      (SRF)-regulated TSPANs in VSMC by using RNA-seq analyses and RNA-arrays. TSPAN2 
      was found to be the only TSPAN family gene induced by TGF-beta1 and MYOCD, and 
      reduced by SRF deficiency in VSMCs. We also found that TSPAN2 is highly expressed 
      in smooth muscle-enriched tissues and down-regulated in in vitro models of VSMC 
      phenotypic modulation. TSPAN2 expression is attenuated in mouse carotid arteries 
      after ligation injury and in failed human arteriovenous fistula samples after 
      occlusion by dedifferentiated neointimal VSMC. In vitro functional studies showed 
      that TSPAN2 suppresses VSMC proliferation and migration. Luciferase reporter and 
      chromatin immunoprecipitation assays demonstrated that TSPAN2 is regulated by 2 
      parallel pathways, MYOCD/SRF and TGF-beta1/SMAD, via distinct binding elements 
      within the proximal promoter. Thus, we identified the first VSMC-enriched and 
      MYOCD/SRF and TGF-beta1/SMAD-dependent TSPAN family member, whose expression is 
      intimately associated with VSMC differentiation and negatively correlated with 
      vascular disease. Our results suggest that TSPAN2 may 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-beta1/SMAD and 
      myocardin/serum response factor.
CI  - (c) FASEB.
FAU - Zhao, Jinjing
AU  - Zhao J
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Wu, Wen
AU  - Wu W
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Lu, Yao Wei
AU  - Lu YW
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Tou, Emiley
AU  - Tou E
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Ye, Jiemei
AU  - Ye J
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Gao, Ping
AU  - Gao P
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Jourd'heuil, David
AU  - Jourd'heuil D
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Singer, Harold A
AU  - Singer HA
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Wu, Mingfu
AU  - Wu M
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA.
FAU - Long, Xiaochun
AU  - Long X
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York, USA longx@mail.amc.edu.
LA  - eng
GR  - R01 HL049426/HL/NHLBI NIH HHS/United States
GR  - R01 HL121700/HL/NHLBI NIH HHS/United States
GR  - R01 HL122686/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170303
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Serum Response Factor)
RN  - 0 (Smad Proteins)
RN  - 0 (TSPAN2 protein, human)
RN  - 0 (Tetraspanins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tspan2 protein, mouse)
RN  - 0 (myocardin)
SB  - IM
MH  - Cell Differentiation
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Male
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Myocytes, Smooth Muscle/physiology
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Serum Response Factor/genetics/*metabolism
MH  - Smad Proteins/genetics/*metabolism
MH  - Tetraspanins/genetics/*metabolism
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcriptome
MH  - Transforming Growth Factor beta1/genetics/*metabolism
PMC - PMC5434656
OTO - NOTNLM
OT  - arteriovenous fistula
OT  - differentiation
OT  - phenotypic modulation
OT  - tetraspanins
EDAT- 2017/03/05 06:00
MHDA- 2017/09/13 06:00
PMCR- 2018/06/01
CRDT- 2017/03/05 06:00
PHST- 2016/09/06 00:00 [received]
PHST- 2017/02/13 00:00 [accepted]
PHST- 2017/03/05 06:00 [pubmed]
PHST- 2017/09/13 06:00 [medline]
PHST- 2017/03/05 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - fj.201601021R [pii]
AID - FJ_201601021R [pii]
AID - 10.1096/fj.201601021R [doi]
PST - ppublish
SO  - FASEB J. 2017 Jun;31(6):2576-2591. doi: 10.1096/fj.201601021R. Epub 2017 Mar 3.