ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
Glutamate enhances the production of inflammatory cytokines IL-6 and IL-11, as well as chemokines CXCL2, CXCL3, and CXCL8 in keloid fibroblasts
Provisionally accepted
- Sir Run Run Shaw Hospital, School of Medicine, Graduate School, Zhejiang University, Hangzhou, China
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Abstract. Keloids are fibroproliferative scars characterized by excessive extracellular matrix deposition and a high tendency for recurrence. No definitive cure is currently available, and the underlying mechanisms remain incompletely understood. Here, we used RNA sequencing (RNA‑seq) to compare gene expression between human keloid tissue and normal skin. We found a distinct enrichment of the neuroactive ligand–receptor interaction pathway and a significant upregulation of the glutamate receptor GRIN2D. Single‑cell sequencing, immunohistochemistry, and immunofluorescence showed that GRIN2D is primarily expressed in fibroblasts. Metabolomic analysis further revealed that the levels of glutamate and glutamine are significantly increased in keloid tissue. In vitro stimulation of fibroblasts with glutamate, combined with RNA‑seq, RT‑PCR, and ELISA, showed that glutamate markedly enhances the secretion of inflammatory cytokines IL‑6 and IL‑11 and the chemokines CXCL2, CXCL3, and CXCL8 (IL‑8). These results underscore the crucial role of glutamate metabolism in promoting the inflammatory functions of fibroblasts. They suggest that glutamate contributes to keloid progression and provides a theoretical basis for targeting glutamte signaling pathway in keloid treatment.
Keywords: fibroblast, Glutamate, GRIN2D, Inflammation, Keloid
Received: 08 Oct 2025; Accepted: 12 Dec 2025.
Copyright: © 2025 Chen, Xu, Zhang, Feng, Chen, Song, Zhu and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hao Cheng
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