Evidence mapPaperPMID 42405671Full record

ArticleInvestigative ophthalmology & visual science2026

Exosome-Associated Gene Network and the Role of SPP1 in Herpes Stromal Keratitis and the Therapeutic Modulation by Ursolic Acid.

Kuiliang Yang, Tingting Fan, Han Zhang, Yulin Yan, Yujin Wang, Jiewen Mao, Zixian Yang, Yanning Yang, Yiqiao Xing, Wanju Yang

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Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

10 authors.

Kuiliang YangAier Eye Hospital of Wuhan University, Wuhan, Hubei Province, China.
Tingting FanAier Eye Hospital of Wuhan University, Wuhan, Hubei Province, China.
Han ZhangAier Eye Hospital of Wuhan University, Wuhan, Hubei Province, China.
Yulin YanEye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Yujin WangEye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Jiewen MaoEye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Zixian YangEye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Yanning YangEye Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Yiqiao XingAier Eye Hospital of Wuhan University, Wuhan, Hubei Province, China.
Wanju YangAier Eye Hospital of Wuhan University, Wuhan, Hubei Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: This study aimed to explore the exosome-related gene network in herpes stromal keratitis (HSK) and to identify key molecular drivers, focusing on the role of secreted phosphoprotein 1 (SPP1) and investigating the therapeutic potential of ursolic acid (UA). Methods: Transcriptomic RNA sequencing was performed on corneal tissues from herpes simplex virus type 1 (HSV-1)-infected mice. Bioinformatics analyses included identification of differentially expressed genes (DEGs), immune cell infiltration assessment, exosome-related gene network construction, functional enrichment analyses, and compound-gene network creation. Immune infiltration findings were further validated using single-cell RNA sequencing and flow cytometry. Key findings were validated in a mouse HSK model using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry. The therapeutic effect and mechanism of UA were investigated through subconjunctival administration, with subsequent evaluation of corneal lesions, angiogenesis, fibrosis, and key signaling pathways. Results: Through analysis, 222 DEGs associated with exosomes were identified in HSK, and the exosome-related gene network revealed that the primary functional cluster was centered on the positive regulation of cell adhesion. Among the genes in the primary functional cluster, SPP1 emerged as a hub gene, demonstrating significant upregulation that correlated with clinical progression. SPP1 expression exhibited a shift from corneal epithelial cells under normal conditions to infiltrating immune cells, particularly neutrophils and monocytes, during HSK. In a mouse model, treatment with UA significantly reduced corneal opacity, vessel in-growth, and inflammatory cell infiltration. Mechanistically, UA downregulated SPP1 expression and subsequently inhibited the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Conclusions: These findings provide new insights into the exosome-related gene network and the mechanisms of HSK, while identifying UA as a promising candidate for therapeutic development.

Indexed as

ExosomesEye Infections, ViralGene Expression RegulationGene Regulatory NetworksKeratitis, HerpeticTriterpenesAnimalsBlotting, WesternCorneal StromaDisease Models, AnimalFemaleFlow CytometryHerpesvirus 1, HumanImmunohistochemistryMiceMice, Inbred C57BLOsteopontinSpp1 protein, mouseTriterpenesUrsolic Acid

Identifiers

PMID42405671
PMCPMC13349020

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.