Sun Siyuan,Cai Na.Role and mechanism of PRMT7 in muscle inflammation,oxidative stress, and fibrosis in Duchenne muscular dystrophy mice[J].Journal of Chongqing Medical University,2025,50(8):1071-1077.
Sun Siyuan,Cai Na.Role and mechanism of PRMT7 in muscle inflammation,oxidative stress, and fibrosis in Duchenne muscular dystrophy mice[J].Journal of Chongqing Medical University,2025,50(8):1071-1077. DOI: 10.13406/j.cnki.cyxb.003742.
Role and mechanism of PRMT7 in muscle inflammation,oxidative stress, and fibrosis in Duchenne muscular dystrophy mice
To investigate the role and mechanism of protein arginine methyltransferase 7(PRMT7) in muscle inflammation,oxidative stress,and fibrosis in Duchenne muscular dystrophy mice.
Methods
2
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
2
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 necrosis factor-α:1071.54±46.63,
F=
55.996,
P
=0.048) and significant 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;gl
utathione/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 increase 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
2
Increasing PRMT7 expression attenuates the inflammation,oxidative stress,and pathological state of fibrosis in the gastrocnemius of mdx mice. Thses effects may be achieved through the PGC-1α/Nrf2 pathway.
关键词
Keywords
references
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