Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.
Serum response factor (SRF) transcriptionally regulates expression of contractile genes in smooth muscle cells (SMC). Lack or decrease of SRF is directly linked to a phenotypic change of SMC, leading to hypomotility of smooth muscle in the gastrointestinal (GI) tract. However, the molecular mechanis...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171262&type=printable |
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| author | Moon Young Lee Chanjae Park Se Eun Ha Paul J Park Robyn M Berent Brian G Jorgensen Robert D Corrigan Nathan Grainger Nathan Grainger Peter J Blair Orazio J Slivano Joseph M Miano Sean M Ward Terence K Smith Kenton M Sanders Seungil Ro |
| author_facet | Moon Young Lee Chanjae Park Se Eun Ha Paul J Park Robyn M Berent Brian G Jorgensen Robert D Corrigan Nathan Grainger Nathan Grainger Peter J Blair Orazio J Slivano Joseph M Miano Sean M Ward Terence K Smith Kenton M Sanders Seungil Ro |
| author_sort | Moon Young Lee |
| collection | DOAJ |
| description | Serum response factor (SRF) transcriptionally regulates expression of contractile genes in smooth muscle cells (SMC). Lack or decrease of SRF is directly linked to a phenotypic change of SMC, leading to hypomotility of smooth muscle in the gastrointestinal (GI) tract. However, the molecular mechanism behind SRF-induced hypomotility in GI smooth muscle is largely unknown. We describe here how SRF plays a functional role in the regulation of the SMC contractility via myotonic dystrophy protein kinase (DMPK) and L-type calcium channel CACNA1C. GI SMC expressed Dmpk and Cacna1c genes into multiple alternative transcriptional isoforms. Deficiency of SRF in SMC of Srf knockout (KO) mice led to reduction of SRF-dependent DMPK, which down-regulated the expression of CACNA1C. Reduction of CACNA1C in KO SMC not only decreased intracellular Ca2+ spikes but also disrupted their coupling between cells resulting in decreased contractility. The role of SRF in the regulation of SMC phenotype and function provides new insight into how SMC lose their contractility leading to hypomotility in pathophysiological conditions within the GI tract. |
| format | Article |
| id | doaj-art-e61d17fcddeb42c798c6f15cef0042fa |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e61d17fcddeb42c798c6f15cef0042fa2025-08-20T03:04:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017126210.1371/journal.pone.0171262Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.Moon Young LeeChanjae ParkSe Eun HaPaul J ParkRobyn M BerentBrian G JorgensenRobert D CorriganNathan GraingerNathan GraingerPeter J BlairOrazio J SlivanoJoseph M MianoSean M WardTerence K SmithKenton M SandersSeungil RoSerum response factor (SRF) transcriptionally regulates expression of contractile genes in smooth muscle cells (SMC). Lack or decrease of SRF is directly linked to a phenotypic change of SMC, leading to hypomotility of smooth muscle in the gastrointestinal (GI) tract. However, the molecular mechanism behind SRF-induced hypomotility in GI smooth muscle is largely unknown. We describe here how SRF plays a functional role in the regulation of the SMC contractility via myotonic dystrophy protein kinase (DMPK) and L-type calcium channel CACNA1C. GI SMC expressed Dmpk and Cacna1c genes into multiple alternative transcriptional isoforms. Deficiency of SRF in SMC of Srf knockout (KO) mice led to reduction of SRF-dependent DMPK, which down-regulated the expression of CACNA1C. Reduction of CACNA1C in KO SMC not only decreased intracellular Ca2+ spikes but also disrupted their coupling between cells resulting in decreased contractility. The role of SRF in the regulation of SMC phenotype and function provides new insight into how SMC lose their contractility leading to hypomotility in pathophysiological conditions within the GI tract.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171262&type=printable |
| spellingShingle | Moon Young Lee Chanjae Park Se Eun Ha Paul J Park Robyn M Berent Brian G Jorgensen Robert D Corrigan Nathan Grainger Nathan Grainger Peter J Blair Orazio J Slivano Joseph M Miano Sean M Ward Terence K Smith Kenton M Sanders Seungil Ro Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. PLoS ONE |
| title | Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. |
| title_full | Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. |
| title_fullStr | Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. |
| title_full_unstemmed | Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. |
| title_short | Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. |
| title_sort | serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and l type calcium channels |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171262&type=printable |
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