GEO series
Identification of fibroblast-derived sFRP2 as a new therapeutic target and engineering of siRNA therapies for uterine scarring
GSE293910
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
12 samples
Submitted 2025/07/06
Platform GPL24247Platform GPL24676
Summary
Uterine scarring (US) is a common complication following uterine injury, characterized by abnormal wound healing in the endometrial or myometrial tissue. However, the underlying mechanisms contributing to scar formation remain unclear, impeding the development of effective drugs for US. Here, we identified that secreted frizzled-related protein 2 (sFRP2) is highly expressed in human and mouse uterine tissues with US, particularly in uterine fibroblasts (UFIBs). Using mouse models, we demonstrated that sFRP2 overexpression in the healthy uterus induced US features and exacerbated surgery-induced scarring, while sFRP2 knockout inhibited US development and scarring-transformation in UFIBs, highlighting the critical role of sFRP2 in mediating US. Mechanistically, sFRP2 promotes uterine scar formation by activating the non-canonical Wnt signaling pathway and calcium influx in UFIBs. Additionally, therapeutic potential of targeting sFRP2 was demonstrated by developing siRNA against sFRP2 and engineering delivery systems of lipid nanoparticles and injectable hydrogel. These siRNA therapies effectively inhibited sFRP2 expression, alleviated uterine scar formation, and improved pregnancy outcomes in mice, underscoring the great potential of sFRP2 as a promising therapeutic target for US.
Published in
Cheng J, Zhang S, Gui Q et al.
· Nature communications 2025
· PMID 40715133
· doi:10.1038/s41467-025-62248-1
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE293910_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1247411. Searching any of these in the dataset finder brings you back here.
Study design
3 × Homo sapiens, uterine myometrial tissue, control, biol vs 3 × Homo sapiens, uterine myometrial tissue, Scar uterus disease group, biol vs 3 × Mus musculus, uterine myometrial tissue, control, biol vs 3 × Mus musculus, uterine myometrial tissue, Scar uterus disease group, biol
Supports a case/control comparison: 6 samples read as cases, 6 as controls.
4 replicated groups read from 12 sample titles; they account for 12 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8893232 Homo sapiens, uterine myometrial tissue, control, biol repl1
- GSM8893233 Homo sapiens, uterine myometrial tissue, control, biol repl2
- GSM8893234 Homo sapiens, uterine myometrial tissue, control, biol repl3
- GSM8893235 Homo sapiens, uterine myometrial tissue, Scar uterus disease group, biol repl1
- GSM8893236 Homo sapiens, uterine myometrial tissue, Scar uterus disease group, biol repl2
- GSM8893237 Homo sapiens, uterine myometrial tissue, Scar uterus disease group, biol repl3
- GSM8893238 Mus musculus, uterine myometrial tissue, control, biol repl1
- GSM8893239 Mus musculus, uterine myometrial tissue, control, biol repl2
- GSM8893240 Mus musculus, uterine myometrial tissue, control, biol repl3
- GSM8893241 Mus musculus, uterine myometrial tissue, Scar uterus disease group, biol repl1
- GSM8893242 Mus musculus, uterine myometrial tissue, Scar uterus disease group, biol repl2
- GSM8893243 Mus musculus, uterine myometrial tissue, Scar uterus disease group, biol repl3
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