Rat cardiac fibroblasts inhibit gap junction between cardiomyocytes through increasing matrix metalloproteinase 2 activity
10.3969/j.issn.1000-4718.2024.03.010
- VernacularTitle:大鼠心肌成纤维细胞通过增加基质金属蛋白酶2活性抑制心肌细胞缝隙连接功能
- Author:
Xue BAI
1
;
Hong GAO
;
Xiang HUANG
;
Xu YAN
;
Tingju HU
;
Rui CHEN
;
Li AN
;
Yuting SONG
Author Information
1. 贵州医科大学麻醉学院,贵州 贵阳 550002
- Keywords:
hypoxia-reoxygenation;
ischemia-reperfusion;
cardiomyocytes;
connexin 43;
matrix metallopro-teinases
- From:
Chinese Journal of Pathophysiology
2024;40(3):465-472
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P＜0.01),narrowed distance of lucifer yellow dif-fusion(P＜0.01),and increased MMP2 activity(P＜0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P＜0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P＜0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.
