Data · dataset · 2025
Hypoxia-driven lactylation facilitates subretinal fibrosis via the H3K18la/RFX8 pathway in profibrotic SPP1+ macrophage
Listed in Teesside University Research Data Repository
Description
This data consists of raw immunoblotting images from the article titled "Hypoxia-driven lactylation facilitates subretinal fibrosis via the H3K18la/RFX8 pathway in profibrotic SPP1+ macrophage".Macular subretinal fibrosis is the end-stage sequela of neovascular age-related macular degeneration (nAMD), leading to irreversible central vision impairment. Although hypoxia is recognized as a key factor contributing to subretinal fibrosis progression, the mechanism by which it drives subretinal fibrosis in nAMD remains poorly understood.
Infiltrating macrophages are crucial for the development of subretinal fibrosis secondary to nAMD. In this study, we demonstrated that hypoxia enhanced lactate production in subretinal fibrotic lesions, and the lactate accumulation further increased histone H3 lysine 18 lactylation in macrophages. Cleavage under targets & tagmentation (CUT&Tag) and transcriptomic analyses revealed that H3K18la promoted fibrosis by upregulating the transcription factor RFX8.
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RFX8, in turn, bound to the secreted phosphoprotein 1 (SPP1) promoter and enhanced its transcription in macrophages, thereby driving the profibrotic macrophages expressing SPP1. These SPP1⁺ macrophages promoted subretinal fibrosis by inducing epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells and activating choroidal fibroblasts. Intraocular-specific knockdown of RFX8 inhibited SPP1 expression and effectively alleviated subretinal fibrosis.
Thus, our study identifies the SPP1-neutralizing antibody MPIIIB10 as a promising therapeutic strategy and delineates the lactate-H3K18la-RFX8 axis in the pathogenesis of subretinal fibrosis.
Links
Where it is published
- DOI doi.org/10.17632/vp473tttkm.1 ↗
DOI / persistent id · from researchdata tees ac uk
Catalogue records · 1
- OAI-PMH record data.mendeley.com/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Adata… ↗
metadata API · from researchdata tees ac uk
Topics
- From keywords
- Earth & Environmental Science
- Inferred from text
- Image 65%
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| Teesside University Research Data Repository | oai:data.mendeley.com/vp473tttkm.1 | 15 h ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| concepts[modality].local:modality:image | enrichment · researchdata tees ac uk | keyword-concept-rules@1.0.0 | title+description (65%) |
| description | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/description |
| license | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/rights |
| publication_date | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | |
| title | source · researchdata tees ac uk | connector:researchdata_tees_ac_uk@1.0.0 | /metadata/dc/title |