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| Status |
Public on Nov 28, 2024 |
| Title |
Connexin 43 dephosphorylation mediates the Dchs1/YAP/TEAD signaling pathway to impact cardiac fibrosis |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The gap junction protein connexin 43 (Cx43) has been implicated in the development of cardiac fibrosis. We found that Cx43 dephosphorylation at serine 282 (S282) is related to cardiomyocyte apoptosis and arrhythmias in hearts damaged by ischemia/reperfusion. Here, we investigated the effect of Cx43 S282 phosphorylation on fibrosis. We found a decrease in Cx43 S282 phosphorylation in transforming growth factor beta-1 (TGF-β)-induced fibrosis in fibroblasts and an angiotensin II-induced rat model. We transferred a lentivirus with S282A (alanine) into cardiac fibroblasts and an adenovirus with S282A into the hearts of rats. We found that the Cx43 S282A mutation caused fibrosis in cardiac fibroblasts and in the hearts of rats, which suggested that the phosphorylation of Cx43 S282 is important in the development of fibrosis. Furthermore, mRNA sequencing showed that Cx43 dephosphorylation at S282 increased the expression of Dchs1, and Dchs1 inhibited Yes-associated protein (YAP) phosphorylation, subsequently activating the YAP/TEAD signaling pathway and increasing the development of fibrosis. This study suggests that the phosphorylation of Cx43 S282 could be an effective antifibrotic target in cardiac fibroblasts, indicating a novel mechanism and a molecular target that might be promising for the treatment of cardiac fibrosis.
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| Overall design |
we sequenced mRNA from injected mouse hearts (Cx43-wt and S282A) using gene set enrichment analysis (GSEA) and the standardized enrichment score (NES). After data analysis, the Hippo signalling pathway was identified as the main pathway involved in p282-Cx43-mediated regulation of MF.
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| Contributor(s) |
Yan X, Gou Z, Wang M, Li W, Shao Y, Huang Y, Wei C, Li P, Sun K |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 05, 2023 |
| Last update date |
Nov 28, 2024 |
| Contact name |
min wang |
| E-mail(s) |
[email protected]
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| Organization name |
Affiliated Suzhou Hospital of Nanjing Medical University
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| Street address |
242 Guangji Road
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| City |
Suzhou |
| ZIP/Postal code |
215008 |
| Country |
China |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (16)
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| GSM7937625 |
sprague-Dawley,control,Day7_v4 |
| GSM7937626 |
sprague-Dawley,Cx43-wt,Day7_w1 |
| GSM7937627 |
sprague-Dawley,Cx43-wt,Day7_w3 |
| GSM7937628 |
sprague-Dawley,Cx43-wt,Day7_w4 |
| GSM7937629 |
sprague-Dawley,Cx43-wt,Day7_w5 |
| GSM7937630 |
sprague-Dawley,S282A,Day7_s1 |
| GSM7937631 |
sprague-Dawley,S282A,Day7_s4 |
| GSM7937632 |
sprague-Dawley,S282A,Day7_s6 |
| GSM7937633 |
sprague-Dawley,S282A,Day7_s7 |
| GSM7937634 |
sprague-Dawley,phosphatase inhibitor Lats-1,Day7_y1 |
| GSM7937635 |
sprague-Dawley,phosphatase inhibitor Lats-1,Day7_y2 |
| GSM7937636 |
sprague-Dawley,phosphatase inhibitor Lats-1,Day7_y4 |
| GSM7937637 |
sprague-Dawley,phosphatase inhibitor Lats-1,Day7_y5 |
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| Relations |
| BioProject |
PRJNA1048890 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249368_gene_fpkm.txt.gz |
3.8 Mb |
(ftp)(http) |
TXT |
| GSE249368_novel_gene.fa.gz |
503.4 Kb |
(ftp)(http) |
FA |
SRA Run Selector |
| Raw data are available in SRA |
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