Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling.
The estrogen inhibits colonic smooth muscle contractions, which may lead to constipation. However, the mechanisms of inhibition are poorly understood. Therefore, the present study examined the effect of estrogen on rat colonic smooth muscle contractions and its potential association with the large-c...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0294249 |
| _version_ | 1797394538983063552 |
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| author | Jing Wen Yu Zhao Cheng Huang Shengjie Li Peidong Li Yu Zhou Zaihua Yan Guangjun Zhang |
| author_facet | Jing Wen Yu Zhao Cheng Huang Shengjie Li Peidong Li Yu Zhou Zaihua Yan Guangjun Zhang |
| author_sort | Jing Wen |
| collection | DOAJ |
| description | The estrogen inhibits colonic smooth muscle contractions, which may lead to constipation. However, the mechanisms of inhibition are poorly understood. Therefore, the present study examined the effect of estrogen on rat colonic smooth muscle contractions and its potential association with the large-conductance Ca2+-activated K+ channels β1 (BKβ1) subunit. Twenty-four female Sprague Dawley rats were randomly assigned to 4 groups. After 2 weeks of intervention, the contraction activity of isolated colonic smooth muscle and the expression of BKβ1 in colonic smooth muscle of rats were detected. Additionally, in order to investigate the effects of estrogen on BKβ1 expression and calcium mobilization, in vitro experiments were conducted using rat and human colonic smooth muscle cells (SMCs). BKβ1 shRNA was used to investigate whether calcium mobilization is affected by BKβ1 in colonic SMCs. To explore the relationship between ERβ and BKβ1, serial deletions, site-directed mutagenesis, a dual-luciferase reporter assay, and chromatin immunoprecipitation assays were employed. In response to E2, colonic smooth muscle strips showed a decrease in tension, while IBTX exposure transiently increased tension. Furthermore, in these muscle tissues, BKβ1 and α-SMA were found to be co-expressed. The E2 group showed significantly higher BKβ1 expression. In cultured colonic SMCs, the expression of BKβ1 was found to increase in the presence of E2 or DPN. E2 treatment reduced Ca2+ concentrations, while BKβ1 shRNA treatment increased Ca2+ concentrations relative to the control. ERβ-initiated BKβ1 expression appears to occur via binding to the BKβ1 promoter. These results indicated that E2 may upregulate BKβ1 expression via ERβ and inhibit colonic smooth muscle contraction through ERβ by directly targeting BKβ1. |
| first_indexed | 2024-03-09T00:21:14Z |
| format | Article |
| id | doaj.art-588327983f6640f6ad8dd6ac47a86661 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-09T00:21:14Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-588327983f6640f6ad8dd6ac47a866612023-12-12T05:34:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011811e029424910.1371/journal.pone.0294249Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling.Jing WenYu ZhaoCheng HuangShengjie LiPeidong LiYu ZhouZaihua YanGuangjun ZhangThe estrogen inhibits colonic smooth muscle contractions, which may lead to constipation. However, the mechanisms of inhibition are poorly understood. Therefore, the present study examined the effect of estrogen on rat colonic smooth muscle contractions and its potential association with the large-conductance Ca2+-activated K+ channels β1 (BKβ1) subunit. Twenty-four female Sprague Dawley rats were randomly assigned to 4 groups. After 2 weeks of intervention, the contraction activity of isolated colonic smooth muscle and the expression of BKβ1 in colonic smooth muscle of rats were detected. Additionally, in order to investigate the effects of estrogen on BKβ1 expression and calcium mobilization, in vitro experiments were conducted using rat and human colonic smooth muscle cells (SMCs). BKβ1 shRNA was used to investigate whether calcium mobilization is affected by BKβ1 in colonic SMCs. To explore the relationship between ERβ and BKβ1, serial deletions, site-directed mutagenesis, a dual-luciferase reporter assay, and chromatin immunoprecipitation assays were employed. In response to E2, colonic smooth muscle strips showed a decrease in tension, while IBTX exposure transiently increased tension. Furthermore, in these muscle tissues, BKβ1 and α-SMA were found to be co-expressed. The E2 group showed significantly higher BKβ1 expression. In cultured colonic SMCs, the expression of BKβ1 was found to increase in the presence of E2 or DPN. E2 treatment reduced Ca2+ concentrations, while BKβ1 shRNA treatment increased Ca2+ concentrations relative to the control. ERβ-initiated BKβ1 expression appears to occur via binding to the BKβ1 promoter. These results indicated that E2 may upregulate BKβ1 expression via ERβ and inhibit colonic smooth muscle contraction through ERβ by directly targeting BKβ1.https://doi.org/10.1371/journal.pone.0294249 |
| spellingShingle | Jing Wen Yu Zhao Cheng Huang Shengjie Li Peidong Li Yu Zhou Zaihua Yan Guangjun Zhang Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. PLoS ONE |
| title | Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. |
| title_full | Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. |
| title_fullStr | Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. |
| title_full_unstemmed | Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. |
| title_short | Estrogen inhibits colonic smooth muscle contractions by regulating BKβ1 signaling. |
| title_sort | estrogen inhibits colonic smooth muscle contractions by regulating bkβ1 signaling |
| url | https://doi.org/10.1371/journal.pone.0294249 |
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