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Status |
Public on Feb 14, 2024 |
Title |
Smurf1 modulates Smad signaling pathway in fibrotic cataract formation [mouse_ASC] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Purpose: TGF-β/BMP signaling pathway has a significant role in fibrotic cataract. Smurf1, a ubiquitin protein ligase, regulates the TGF-β/BMP signaling pathway through the ubiquitin-proteasome system (UPS). This study aims to investigate the role of Smurf1 in the progression of fibrotic cataract and its underlying mechanism.Method: We employed a mouse injury-induced anterior subcapsular cataract (ASC) model and administered Smurf1 inhibitor A01 through anterior chamber injection for in vivo investigation. RNA sequencing was performed to examine global gene expression changes. The volume of the subcapsular opacity was determined using whole-mount immunofluorescence of lens anterior capsules. Lentivirus was utilized to create cell lines with Smurf1 knockdown or overexpression in SRA01/04. Protein levels were assessed by Simple Western. Lens epithelial cell (LEC) proliferation was evaluated by CCK8 and EdU assays. LEC migration was measured by Transwell and wound healing assays.Results: The mRNA levels of genes associated with cell proliferation, migration, epithelial-mesenchymal transition (EMT), TGF-β/BMP pathway and UPS, including Smurf1, were upregulated in ASC model. The mRNA expression of Smurf1 was also upregulated in anterior lens capsules of age-related cataract patients. Anterior chamber injection of A01 inhibited ASC formation and EMT. In vitro knockdown of Smurf1 resulted in reduced proliferation, TGF-β2-induced migration and EMT of LECs. Smurf1 inhibition upregulated Smad1, Smad5 and pSmad1/5. Conversely, Smurf1 overexpression displayed the opposite phenotypes.Conclusion: Smurf1 regulated the progression of fibrotic cataract by influencing the proliferation, migration and EMT of LECs through regulation of Smad signaling pathway, offering a novel target for the treatment of fibrotic cataract.
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Overall design |
To evaluate the overall change of gene expression in fibrotic cataract, we conducted RNA-sequencing on lens capsules collected from an injury-induced ASC mouse model seven days after surgery. Lens capsules from mice that underwent a sham operation, involving only corneal incision without lens capsule incision, served as the control group. Each group has four biological replicates.
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Contributor(s) |
Jiang F |
Citation(s) |
38324299 |
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Submission date |
Oct 15, 2023 |
Last update date |
Feb 14, 2024 |
Contact name |
Fanying Jiang |
E-mail(s) |
jiangfy3@mail2.sysu.edu.cn
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Phone |
+8615521187291
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Organization name |
Zhongshan Ophthalmic Center, Sun Yat-Sen University
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Street address |
No. 7, Jinsui Road
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City |
Guangzhou |
ZIP/Postal code |
510060 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (8)
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This SubSeries is part of SuperSeries: |
GSE245412 |
Smurf1 modulates Smad signaling pathway in fibrotic cataract formation |
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Relations |
BioProject |
PRJNA1028297 |
Supplementary file |
Size |
Download |
File type/resource |
GSE245411_gene_count.txt.gz |
443.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
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