MicroRNA-135a is up-regulated and aggravates myocardial depression in sepsis via regulating p38 MAPK/NF-κB pathway.
MicroRNA-135a (miR-135a) is implicated in the pathological processes of several cancers. However, the roles and regulatory mechanism of miR-135a in sepsis-induced myocardial depression (MD) remain largely unknown. In this study, the serum of patients with sepsis and healthy controls was obtained. The miR-135a expression was then measured. Then lentiviruses (miR-135a mimic, inhibitor and scramble control) were transfected into BALB/c mice. After 4days of transfection, polymicrobial sepsis model was established by cecal ligation and puncture (CLP) surgery. The serum tumor-necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were detected. Cardiac function was assessed. In addition, the protein expressions of p38 MAPK/NF-κB pathway-related proteins were determined. Besides, SB203580 and JSH-23, the inhibitors of p38 MAPK and NF-κB respectively, were used to treat the isolated ventricular myocytes in vitro. MiR-135a was significantly up-regulated in the serum of patients with sepsis. In comparison with CLP group, the concentrations of TNF-α, IL-1β and IL-6 and the expressions of p-p38 and p-p65 in CLP+miR-135a mimic group were significantly increased, while markedly decreased in CLP+miR-135a inhibitor group. Moreover, EF, FS, LVdP/dt (max), LVdP/dt (min) and LVDP of CLP+miR-135a mimic group were all significantly decreased, while markedly increased in CLP+miR-135a inhibitor group. Besides, the increased expressions of p-p38 and p-p65, decreased expression of p-IKBα and the decreased percentage of contraction amplitude in miR-135a mimic group were markedly reversed by SB203580 or JSH-23 treatments. Up-regulation of miR-135a could aggravate sepsis-induced inflammation and myocardial dysfunction via activation of p38 MAPK/NF-κB pathway.
Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, China.
Ge
G
Zheng
Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, China.
Minli
M
Pan
Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, China.
Weimin
W
Jin
Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, China.
Guoxin
G
Jin
Department of Pediatrics, Ruian People's Hospital, Ruian, Zhejiang 325200, China. Electronic address: yumaohuang08@126.com.
Yumao
Y
Huang
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D009202:Cardiomyopathies / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
MicroRNA-135a; Myocardial depression; Sepsis; p38 MAPK/NF-κB pathway