Role and mechanism of PRMT7 in muscle inflammation,oxidative stress,and fibrosis in Duchenne muscular dystrophy mice
10.13406/j.cnki.cyxb.003742
- VernacularTitle:PRMT7在Duchenne肌营养不良小鼠肌肉炎症、氧化应激和纤维化中的作用及机制研究
- Author:
Siyuan SUN
1
;
Na CAI
Author Information
1. 西北妇女儿童医院儿童保健科,西安 710061
- Keywords:
muscular dystrophy;
protein arginine methyltransferase 7;
inflammation;
fibrosis;
peroxisome proliferator-activated recep-tor gamma coactivator-1 alpha;
nuclear factor erythroid 2-related factor 2
- From:
Journal of Chongqing Medical University
2025;50(8):1071-1077
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and mechanism of protein arginine methyltransferase 7(PRMT7)in muscle inflamma-tion,oxidative stress,and fibrosis in Duchenne muscular dystrophy mice.Methods:In this study,C57BL/6 wild-type mice were used as the control group,mdx mice as the model group of Duchenne muscular dystrophy,and mdx mice injected with AAV9-PRMT7 by the caudal vein as the experimental group.The levels of inflammatory factors were measured by an enzyme-linked immunosorbent assay.Oxidative stress-related indicators were measured using commercial kits.Masson staining was performed to assess the fibrosis degree of the gastrocnemius.The expression of PRMT7,peroxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1α),and nuclear factor erythroid 2-related factor 2(Nrf2)was analyzed by a Western blot assay.The arginine methylation level of PGC-1α was determined by an immunoprecipitation assay.Results:PRMT7 expression was significantly reduced in the gastrocnemius of mdx mice(0.67±0.03,F=70.764,P=0.001).The up-regulation of PRMT7 resulted in significant decreases in the levels of inflammatory factors(interleukin-1β:167.87±13.25,F=407.751,P<0.001;tumor ne-crosis factor-α:1071.54±46.63,F=55.996,P=0.048)and signifi-cant improvements in the oxidative stress and fibrosis status in the gastrocnemius of mdx mice(reactive oxygen species:1.16±0.03,F=86.820,P=0.008;malondialdehyde:66.11±3.84,F=228.175,P=0.001;glutathione/oxidized glutathione:2.53±0.06,F=499.962,P<0.001;fibrosis area:10.33±0.47,F=604.272,P=0.002),an in-crease in the arginine methylation level of PGC-1α,and significant increases in protein levels of PGC-1α and Nrf2(PGC-1α:1.94±0.11,F=31.565,P=0.038;Nrf2:1.53±0.12,F=140.761,P<0.001).Conclusion:Increasing PRMT7 expression attenuates the inflam-mation,oxidative stress,and pathological state of fibrosis in the gastrocnemius of mdx mice.Thses effects may be achieved through the PGC-1α/Nrf2 pathway.
