التفاصيل البيبلوغرافية
| العنوان: |
Regulation of the Muscarinic M3 Receptor by Myocardin-Related Transcription Factors |
| المؤلفون: |
Liu, Li, Rippe, Catarina, Hansson, Ola, Kryvokhyzha, Dmytro, Fisher, Steven, Ekman, Mari, Swärd, Karl |
| المساهمون: |
Swedish Research Council, Swedish Foundation for Strategic Research |
| المصدر: |
Frontiers in Physiology ; volume 12 ; ISSN 1664-042X |
| بيانات النشر: |
Frontiers Media SA |
| سنة النشر: |
2021 |
| المجموعة: |
Frontiers (Publisher - via CrossRef) |
| مصطلحات موضوعية: |
Physiology (medical), Physiology |
| الوصف: |
Myocardin-related transcription factors (MRTFs: myocardin/ MYOCD , MRTF-A/ MRTFA , and MRTF-B/ MRTFB ) are co-factors of serum response factor (SRF) that activate the smooth muscle cell (SMC) gene program and that play roles in cardiovascular development and mechanobiology. Gain and loss of function experiments have defined the SMC gene program under control of MRTFs, yet full understanding of their impact is lacking. In the present study, we tested the hypothesis that the muscarinic M 3 receptor ( CHRM3 ) is regulated by MRTFs together with SRF. Forced expression of MYOCD (8d) in human coronary artery (SMC) followed by RNA-sequencing showed increased levels of M 2 , M 3 , and M 5 receptors ( CHRM2 : 2-fold, CHRM3 : 16-fold, and CHRM5 : 2-fold). The effect of MYOCD on M 3 was confirmed by RT-qPCR using both coronary artery and urinary bladder SMCs, and correlation analyses using human transcriptomic datasets suggested that M 3 may also be regulated by MRTF-B. Head-to-head comparisons of MYOCD, MRTF-A and MRTF-B, argued that while all MRTFs are effective, MRTF-B is the most powerful transactivator of CHRM3 , causing a 600-fold increase at 120h. Accordingly, MRTF-B conferred responsiveness to the muscarinic agonist carbachol in Ca 2+ imaging experiments. M 3 was suppressed on treatment with the MRTF-SRF inhibitor CCG-1423 using SMCs transduced with either MRTF-A or MRTF-B and using intact mouse esophagus in culture (by 92±2%). Moreover, silencing of SRF with a short hairpin reduced CHRM3 (by >60%) in parallel with α-actin ( ACTA2 ). Tamoxifen inducible knockout of Srf in smooth muscle reduced Srf (by 54±4%) and Chrm3 (by 41±6%) in the urinary bladder at 10days, but Srf was much less reduced or unchanged in aorta, ileum, colon, trachea, and esophagus. Longer induction (21d) further accentuated the reduction of Chrm3 in the bladder and ileum, but no change was seen in the aorta. Single cell RNA-sequencing revealed that Mrtfb dominates in ECs, while Myocd dominates in SMCs, raising the possibility that Chrm3 ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| DOI: |
10.3389/fphys.2021.710968 |
| DOI: |
10.3389/fphys.2021.710968/full |
| الإتاحة: |
https://doi.org/10.3389/fphys.2021.710968Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.BAD22AF1 |
| قاعدة البيانات: |
BASE |
