{
  "abstract": "Elevated levels of IL-8 have been detected in the vitreous samples of patients with diabetic retinopathy. However, its role in retinal neovascularization remains unknown. We hypothesized that IL-8 and its murine orthologues, CXCL1/2, are key mediators of oxygen-induced retinopathy (OIR)-driven retinal angiogenesis. To this end, we found that VEGFA stimulates CXCL1/2 and their receptor CXCR2 expression in mouse retinal microvascular endothelial cells (MRMVECs) in a time-dependent manner. Recombinant CXCL1/2 induced MRMVEC migration, proliferation, sprouting, and tube formation alone and in combination. Neutralizing CXCL1/2 or CXCR2 antibodies (Abs) attenuated the angiogenic effects of CXCL1/2 as well as VEGFA. In line with these observations in mice, VEGFA induced IL-8 and its receptor CXCR2 expression in human retinal microvascular endothelial cells (HRMVECs), and neutralizing IL-8 or CXCR2 Abs suppressed their angiogenic effects. Furthermore, OIR induced CXCL1/2 and CXCR2 expression in the mouse retina in vivo, and blockade of their function using their neutralizing Abs reduced retinal neovascularization. Mechanistically, depletion of ATF6 or GRP78 levels abrogated VEGFA-induced CXCL1/2 and CXCR2 expression in MRMVECs and IL-8 and CXCR2 expression in HRMVECs in vitro and OIR-induced CXCL1/2 and CXCR2 expression in vivo in mice. Furthermore, silencing VEGFR2 or VEGFR3 levels inhibited VEGFA/OIR-induced ATF6-GRP78 activation and their downstream CXCL1/2, IL-8 and CXCR2 expression both in vitro and in vivo. Together, these findings identify IL-8 as potential therapeutic target for treating retinal neovascular diseases.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10456-026-10104-1.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology, University of Tennessee Health Science Center, 71 S Manassas Street, Memphis, TN 38163 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chandra Sekhar Yadavalli"
    },
    {
      "affs": [
        0
      ],
      "name": "Raj Kumar"
    },
    {
      "affs": [
        0
      ],
      "name": "Suresh Govatati"
    },
    {
      "affs": [
        0
      ],
      "name": "Gadiparthi N. Rao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3dycbh8tfg9dm.bib",
  "cited_by": 0,
  "doi": "10.1007/s10456-026-10104-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696613/",
  "id": "3dycbh8tfg9dm",
  "issns": [
    "0969-6970",
    "1573-7209"
  ],
  "landing_url": "https://doi.org/10.1007/s10456-026-10104-1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Paper"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7223575024",
  "pdf_url": "https://europepmc.org/articles/PMC13696613?pdf=render",
  "pmcid": "PMC13696613",
  "pmid": "42927510",
  "published": "2026-10-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3dycbh8tfg9dm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "PMC13696613",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10456-026-10104-1"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927510",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927510"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "VEGFR2-dependent VEGFR3 expression leads to CXCL1/2 and CXCR2 induction in the development of retinal neovascularization",
  "title_text": "VEGFR2-dependent VEGFR3 expression leads to CXCL1/2 and CXCR2 induction in the development of retinal neovascularization",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:55Z",
  "url": "https://research.draconitic.com/paper/3dycbh8tfg9dm",
  "venue": "Angiogenesis",
  "versions": []
}