Prostaglandin E2-mediated aging microenvironment fuels pathogenic fibrosis in cesarean section scar defect.

Yin Y, Chen H, Xie W, Wang Y, Qian Y, Sheng R, Li D, Li J, Zhou X, Dai Z, Mao Z, Li Z, Wang X
EMBO molecular medicine · 2026 · doi:10.1038/s44321-026-00521-6 · PMID:42827157 · PMC13748614
OA: gold CC-BY-4.0
📄 Open PDF View on PubMed View at publisher

Abstract

With the increasing rates of cesarean section (CS), cesarean section scar defect (CSD) has become an escalating clinical concern due to uterine dysfunction and reduced fertility. However, the biological basis of CSD remains poorly understood, particularly the mechanisms of impaired uterine repair after CS and the causes of failure in conventional repair surgeries. This study integrates metabolomics, transcriptomics, a newly developed mouse model, and functional assays to elucidate the complex interplay between senescence and fibrosis in CSD. Our findings identify upregulation of the PGES/prostaglandin E2 (PGE2) axis as a key upstream event that disrupts uterine healing. Elevated PGE2 preferentially induces early senescence of macrophages, which transmit pro-senescent signals to uterine fibroblasts through IL-1β/IL-1R signaling. This sequential senescence cascade drives excessive fibroblast activation and progressive fibrosis, ultimately impairing uterine structure and function. In mouse CS models, inhibition of the PGES/PGE2 pathway and anti-aging strategies significantly attenuate fibrosis and restore coordinated myometrial and endometrial repair. Our findings uncover a macrophage-fibroblast senescence relay to fibrotic scar formation in CSD and provide a translational rationale for targeting PGE2 signaling and senescence to improve uterine repair after CS.

My notes (saved in your browser only)

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

SciLite annotations

chemicals 59
levonorgestrel prostaglandin e2 arachidonic acid nitrogen nitrogen methanol arachidonic acid arachidonic acid arachidonic acid prostaglandin thromboxane lysophosphatidic acids lipid progesterone taurohyodeoxycholic acid water pentobarbital sodium penicillin celecoxib metformin ethanol methylene blue penicillin streptomycin cisplatin etoposide celecoxib alexa fluor 488 formaldehyde haematoxylin prostaglandin nitrogen prostaglandin e2 prostaglandin arachidonic acid prostaglandin arachidonic acid arachidonic acid progesterone taurohyodeoxycholic acid progesterone celecoxib celecoxib prostaglandin etoposide imatinib quercetin metformin metformin metformin metformin progesterone oxygen prostaglandin metformin metformin prostaglandin e2 prostaglandin e2
organisms 67
human human human rodents rodents rodents rodents mus sp. rodents multicellular animals transgenic mice mus sp. mus sp. mus sp. mus sp. mus sp. multicellular animals zea saccharata zea saccharata zea saccharata transgenic mice zitter rats mus migratorius mus sp. mus sp. mus sp. mus sp. transgenic mice human human human human human human rabbits human naine d'afrique de l'ouest rabbits human zitter rats transgenic mice humans human transgenic mice mus sp. mus sp. mus sp. mus sp. mus sp. mus sp. mus sp. adeno-associated virus mus sp. mus sp. human human transgenic mice transgenic mice transgenic mice transgenic mice +7 more

Source provenance

europepmc
last seen: 2026-11-15T09:34:25.365398+00:00
scilite
last seen: 2026-11-15T10:16:09.319260+00:00
License: CC-BY-4.0 · commercial use OK · attribution required
Per Europe PMC