Background: Myocardial Fibrosis (MF) is an important physiological change after
myocardial infarction (MI). MicroRNA-26b (MiR-26b) has a certain inhibitory effect on pulmonary
fibrosis. However, the role of miR-26b in MI-induced MF rats and underlying molecular
mechanisms remain unknown.
Methods: Forty male Sprague Dawley (SD) rats weighing 200-250 g were divided into four groups
(n=10): Sham group, MF group, MF + negative control (NC) agomir group and MF + miR-26b
agomir group. Cardiac fibroblasts were isolated from cardiac tissue. Fibrosis levels were detected
by MASSON staining, while the expression of related genes was detected by RT-qPCR, Western
blotting and Immunohistochemistry, respectively. TargetScan and dual-luciferase reporter assay
were utilized to predict the relationship between miR-26b and high mobility group, AT-hook 2
Results: The study found the expression of miR-26b to be down-regulated in the myocardium of
MF rats (P<0.01). miR-26b overexpression in vitro significantly reduced the survival rate of cardiac
fibroblasts and inhibited the expression of the fibrillar-associated protein (α-SMA alphasmooth
muscle actin (α-SMA) and collagen I) (P<0.01). TargetScan indicated that HMGA2 was
one of the target genes of miR-26b; dual-luciferase reporter assay further confirmed the targeted
regulatory relationship (P<0.01). Moreover, miR-26b overexpression significantly reduced the expression
of HMGA2 (P<0.01). Notably, HMGA2 overexpression reversed the inhibitory effect of
miR-26b overexpression on cardiac fibroblast viability and the expression of α-SMA and collagen
I (P<0.01). Animal experiments further indicated that miR-26b overexpression inhibited MIinduced
rat MF by inhibiting the expression of HMGA2 (P<0.05, P<0.01).
Conclusion: In short, these findings indicate that miR-26b targets HMGA2 to ameliorate
MI-induced fibrosis by suppression of cardiac fibroblasts activation.