Complement C3 is involved in the recruitment and activation of mast cells during renal interstitial fibrosis
10.3760/cma.j.cn441217-20240430-00446
- VernacularTitle:补体C3在肾间质纤维化过程中参与募集、活化肥大细胞
- Author:
Yanping FENG
1
;
Zhenzhou LI
;
Jiong CUI
;
Xiaoting WU
;
Liyan YANG
;
Jianxin WAN
Author Information
1. 福州市第二总医院肾内科，福州 350007
- Publication Type:Journal Article
- Keywords:
Complement C3;
Fibrosis;
Mast cells;
Renal interstitial
- From:
Chinese Journal of Nephrology
2024;40(12):952-960
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the role of complement C3 in the process of renal interstitial fibrosis.Methods:Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient (C3KO) mice and age-matched C57BL/6 wild type (WT) mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in WT group (WTcontrol) ( n=6), UUO operation in WT group (WTuuo) ( n=6), sham operation in C3-deficient group (C3KOcontrol) ( n=6), and UUO operation in C3-deficient group (C3KOuuo) ( n=6). Tubular interstitial fibrosis was observed by both HE staining and Masson staining. The expression of C3, trypsin (tryptase), angiotensinⅡ (AngⅡ), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) was detected by immunohistochemical staining. Chymase level were assessed by immunofluorescence staining. The levels of AngⅡ and C3 cleavage fragments C3a and MMP-9 were determined by enzyme-linked immunosorbent assay. The change in renin mRNA was determined by real-time PCR. The changes of chymase, renin, and TGF-β1 were detected by Western blotting. Results:Compared with the WTcontrol group mice, the WTuuo group mice showed significant renal tubular injury, renal interstitial fibrosis, increased infiltration of mast cells, and significantly increased expression of C3, C3a, chymase, renin, AngⅡ, TGF-β1, and MMP-9 in the renal tissue (all P<0.05). Compared with the WTuuo group mice, the renal tubular injury and renal interstitial fibrosis in the C3KOuuo group mice were significantly reduced, and C3 and C3a were not detected in renal tissue. Mast cells infiltration was reduced, and the expression of chymase, renin, AngⅡ, TGF-β1, and MMP-9 was weakened (all P<0.05). Conclusion:C3/C3a can participate in the recruitment and activation of mast cells to release chymase in kidney interstitial fibrosis, and promote the expression of renin, AngⅡ, TGF-β1, MMP 9 and other substances, thus aggravating kidney injury.
