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<p>Epidermal growth factor receptor (EGFR) signalling plays a crucial role in renal fibrosis. We previously demonstrated that EGFR mimotope vaccination could alleviate renal fibrosis by restoring major histocompatibility complex class IB (MHC-IB) expression in renal tubular epithelial cells and promoting MHC-IB-enriched exosome release. Intriguingly, the mechanism by which the EGFR mimotope affects MHC-IB remains unknown. In this study, we demonstrated that administering purified EGFR mimotope-induced antibodies (EM-pAb) can effectively upregulate ribosomal protein ligand (RPL)-6, poly (rC) binding protein 2 (PCBP2), and MHC-IB in tubular epithelial cells. Mechanistically, the EM-pAb promoted EGFR/ribosomal protein ligand 6 (RPL6)/poly (rC) binding protein 2 (PCBP2) functional ternary complex formation, re-established the binding capability of PCBP2 to MHC-IB β-chain, and further regulated the NK cell population. RPL6 was confirmed as the key orchestrator of the ternary complex formation. <i>Rpl6</i><sup>CKI</sup> mice further revealed the protective role of RPL6 in the animal model of renal fibrosis. RPL6 and kidney function showed a significant correlation in patients with chronic kidney disease. Overall, our findings uncover the signalling pathway by which EGFR modulates MHC-IB and validate the regulatory role of EM-pAb in this signalling pathway, indicating the therapeutic potential of RPL6 in chronic kidney disease.</p>

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EGFR mimotope alleviates renal fibrosis by promoting EGFR/RPL6/PCBP2 ternary complex formation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月4日

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  • Qing Wu,
  • Yu Chen,
  • Di Zhao,
  • Yuxuan Zhou,
  • Zhenhao Yang,
  • Xiaojing Zhong,
  • Jianying Niu,
  • Lin Yang

摘要

Epidermal growth factor receptor (EGFR) signalling plays a crucial role in renal fibrosis. We previously demonstrated that EGFR mimotope vaccination could alleviate renal fibrosis by restoring major histocompatibility complex class IB (MHC-IB) expression in renal tubular epithelial cells and promoting MHC-IB-enriched exosome release. Intriguingly, the mechanism by which the EGFR mimotope affects MHC-IB remains unknown. In this study, we demonstrated that administering purified EGFR mimotope-induced antibodies (EM-pAb) can effectively upregulate ribosomal protein ligand (RPL)-6, poly (rC) binding protein 2 (PCBP2), and MHC-IB in tubular epithelial cells. Mechanistically, the EM-pAb promoted EGFR/ribosomal protein ligand 6 (RPL6)/poly (rC) binding protein 2 (PCBP2) functional ternary complex formation, re-established the binding capability of PCBP2 to MHC-IB β-chain, and further regulated the NK cell population. RPL6 was confirmed as the key orchestrator of the ternary complex formation. Rpl6CKI mice further revealed the protective role of RPL6 in the animal model of renal fibrosis. RPL6 and kidney function showed a significant correlation in patients with chronic kidney disease. Overall, our findings uncover the signalling pathway by which EGFR modulates MHC-IB and validate the regulatory role of EM-pAb in this signalling pathway, indicating the therapeutic potential of RPL6 in chronic kidney disease.