Epidermal growth factor receptor mimotope alleviates renal fibrosis in murine unilateral ureteral obstruction model

• Published in: Clinical immunology (Orlando, Fla.) Vol. 205; pp. 57 - 64
• Main Authors: Yang, Lin, Yuan, Haoran, Yu, Ying, Yu, Nan, Ling, Lilu, Niu, Jianying, Gu, Yong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019
• Subjects: Actins - drug effects; Actins - metabolism; Animals; Apoptosis - drug effects; CD9; Collagen Type I - drug effects; Collagen Type I - metabolism; Disease Models, Animal; Epidermal growth factor receptor; ErbB Receptors - drug effects; ErbB Receptors - immunology; ErbB Receptors - metabolism; Fibronectins - drug effects; Fibronectins - metabolism; Fibrosis; Kidney - drug effects; Kidney - immunology; Kidney - pathology; Macrophage; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; Mice; Mimotope; Molecular Mimicry; Peptides - immunology; Peptides - pharmacology; Renal fibrosis; Ureteral Obstruction - pathology; Vaccination - methods; Renal fibrosis; CFA/IFA; Epidermal growth factor receptor; EGFR; ECM; UUO; MMP; ADAM; ALCAM; Mimotope; CD9; CKD; Macrophage
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2019.05.014

Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In current study, we sought to observe whether the active immunization induced by the EGFR mimotope could ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model. Meanwhile, the EGFR mimotope immunization could inhibit the EGFR downstream signaling. Additionally, the frequency of and F4/80+CD9+/FAS+ macrophages significantly increased in spleen after the EGFR mimotope immunization. These evidence suggested that the EGFR mimotope could alleviate renal fibrosis by both inhibiting EGFR signaling and promoting macrophages apoptosis. •The EGFR mimotope can ameliorate renal fibrosis in the animal model.•The EGFR mimotope can reduce the macrophages in the kidney and spleen.•The EGFR mimotope can up-regulate CD9 and FAS in the macrophages.