Mechanism of PADI4-mediated negative regulation of neutrophil MMP-14/17/25 expression in systemic lupus erythematosus
10.19405/j.cnki.issn1000–1492.2026.09.008
- VernacularTitle:PADI4负向调控中性粒细胞MMP-14/17/25表达在系统性红斑狼疮中的机制
- Author:
Ying LUO
1
;
Xiaoqing WANG
1
;
Jie MA
1
;
Qiang ZHOU
1
Author Information
1. Department of Clinical Laboratory， The Second Affiliated Hospital of Anhui Medical University， Hefei 230601
- Publication Type:Journal Article
- Keywords:
systemic lupus erythematosus;
matrix metalloproteinases;
peptidyl arginine deiminase 4;
neutrophils;
cell migration
- From:
Acta Universitatis Medicinalis Anhui
2026;61(9):1568-1575
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the regulatory mechanism of peptidylarginine deiminase 4 （PADI4） on matrix metalloproteinase （MMPs） expression and its potential role in the development of systemic lupus erythematosus （SLE）. MethodsThe mRNA expression levels of MMP-14/17/25 in SLE patients and healthy controls （HC） were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR）， and their serum protein levels were measured by enzyme-linked immunosorbent assay （ELISA）. Spearman's rank correlation analysis was used to evaluate the correlations between MMPs levels and clinical parameters in SLE patients. Primary neutrophils were treated with the PADI4 inhibitor GSK484， or MMPs expression levels were examined in PADI4-knockdown neutrophil-like HL-60 （dHL-60） cells， and cell migration ability was assessed by wound healing assay. ResultsThe mRNA expression levels of MMP-14/17/25 in neutrophils from SLE patients were lower than those in the HC （all P<0.01）. Serum levels of these three MMPs were also lower than those in the HC （all P<0.01）. MMP-14 levels were negatively correlated with immunoglobulin G （IgG） （r=-0.266）， immunoglobulin A （IgA） （r=-0.286）， and globulin （GLB）（r=-0.269） （all P<0.05）， while both MMP-17 （r=-0.269） and MMP-25（r=-0.244） levels were negatively correlated with urinary protein （UTP） （all P<0.05）. After treatment with GSK484 （10 μmol/L） to inhibit PADI4 activity， the protein expression levels of MMP-14/17/25 in neutrophils were higher than those in the Vehicle group （all P<0.05）， and the cell migration rate in wound healing assay was also greater than that in the Vehicle group （P<0.01）. Furthermore， after knockdown of PADI4 expression， the mRNA expression levels of MMP-14/17/25 were higher than those in the Vehicle group （all P<0.05）. ConclusionMMP-14/17/25 are downregulated in SLE and negatively regulated by PADI4. PADI4 may contribute to SLE progression by suppressing MMPs expression and neutrophil migration. These findings suggest that MMPs may serve as novel biomarkers and therapeutic targets for SLE.
