Background:
MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury.
Methods:
Lipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 (
ROCK1
), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified.
Results:
In the rat model, miR-23a was poorly expressed in myocardial (sham
vs
. sepsis 1.00 ± 0.06
vs.
0.27 ± 0.03,
P
< 0.01) and kidney tissues (sham
vs.
sepsis 0.27 ± 0.03
vs.
1.00 ± 0.06,
P
< 0.01). Artificial overexpression of miR-23a resulted in increased proliferative activity (DNA replication rate: Control
vs.
LPS
vs.
LPS + Mock
vs.
LPS + miR-23a: H9C2 cells: 34.13 ± 3.12
vs.
12.94 ± 1.21
vs.
13.31 ± 1.43
vs.
22.94 ± 2.26,
P
< 0.05; HK-2 cells: 15.17 ± 1.43
vs.
34.52 ± 3.46
vs.
35.19 ± 3.12
vs.
19.87 ± 1.52,
P
< 0.05), decreased cell apoptosis (Control
vs.
LPS
vs.
LPS + Mock
vs.
LPS + miR-23a: H9C2 cells: 11.39 ± 1.04
vs.
32.57 ± 2.29
vs.
33.08 ± 3.12
vs.
21.63 ± 2.35,
P
< 0.05; HK-2 cells: 15.17 ± 1.43
vs.
34.52 ± 3.46
vs.
35.19 ± 3.12
vs.
19.87 ± 1.52,
P
< 0.05), and decreased production of inflammatory cytokines, including interleukin-6 (Control
vs.
LPS
vs.
LPS + Mock
vs.
LPS + miR-23a: H9C2 cells: 59.61 ± 5.14
vs.
113.54 ± 12.30
vs.
116.51 ± 10.69
vs.
87.69 ± 2.97 ng/mL;
P
< 0.05,
F
= 12.67, HK-2 cells: 68.12 ± 6.44
vs.
139.65 ± 16.62
vs.
143.51 ± 13.64
vs.
100.82 ± 9.74 ng/mL,
P
< 0.05,
F
...