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Article

Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway

  • Authors:
    • Yongzhe Guo
    • Linyan Chen
    • Shumei Li
    • Xintao Zhang
    • Huizhong Lin
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Medical Center for Cardiovascular Diseases, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
  • Article Number: 140
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    Published online on: March 20, 2026
       https://doi.org/10.3892/mmr.2026.13850
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Abstract

The present study investigated the role of Lys‑63‑specific deubiquitinase BRCC36 (BRCC36) in preventing cardiac rupture following acute myocardial infarction (AMI) through the Wnt/β‑catenin signaling pathway. Cardiomyocyte‑specific BRCC36‑overexpressing transgenic mice (α‑MHC‑BRCC36) and their wild‑type littermates were used. Experimental mice were allocated into five distinct groups: Sham, AMI, sham + BRCC36, AMI + BRCC36 and AMI + BRCC36 + Wnt groups. The experimental groups subsequently underwent comprehensive assessment of cardiac parameters including cardiac function, hemodynamics, myocardial infarct size, apoptosis and tissue pathology. The AMI + BRCC36 group showed predominantly resolved lesions, minimal inflammatory infiltration and limited collagen fiber degradation compared with the AMI model group, which resulted in improved cardiac function and a reduction in infarct size, apoptosis and fibrosis. The protective effects of BRCC36 were compromised by the addition of Wnt5a, a member of the Wnt family involved in the Wnt/β‑catenin signaling pathway, which is important for cardiac function. No significant differences were observed between the sham and sham + BRCC36 groups. Compared with the sham groups, AMI mice sustained severe impairments in cardiac systolic/diastolic function, alongside enlarged infarct size, increased cardiomyocyte apoptosis and exacerbated myocardial fibrosis. These deleterious effects were markedly attenuated by BRCC36 overexpression, as evidenced by improved cardiac function, reduced infarct size and apoptosis and attenuated fibrosis. Notably, the cardioprotective effects of BRCC36 were substantially abolished by co‑administration of a Wnt agonist. At the molecular level, BRCC36 overexpression suppressed the activation of the Wnt/JNK/c‑Jun signaling pathway (as indicated by decreased levels of Wnt5a, p‑c‑Jun and p‑JNK) induced by AMI, whereas Wnt agonist treatment reversed this suppression. BRCC36 overexpression was therefore shown to inhibit cardiomyocyte apoptosis, diminish myocardial infarct size, suppress myocardial fibrosis and improve cardiac function in a mouse model of AMI, possibly by suppressing Wnt/JNK signaling pathway activation.
View Figures

Figure 1

Myocardial infarct size across mouse
experimental groups. (A) Representative images of
2,3,5-triphenyltetrazolium chloride-stained myocardial cross
sections. Viable myocardium stained red, whereas infarct areas
appeared pale. (B) Quantitative analysis of infarct size, expressed
as area of myocardial infarct (%). Data are presented as mean ± SD
and statistical significance was analyzed by one-way ANOVA followed
by Tukey's post hoc test. *P<0.05 vs. sham group;
#P<0.05 vs. AMI group; ∆P<0.05 vs. AMI
+ BRCC36 group. AMI, acute myocardial infarction; BRCC36,
Lys-63-specific deubiquitinase BRCC36.

Figure 2

Cardiomyocyte apoptosis rate of mice
cardiomyocytes in each group. (A) Representative images of
TUNEL-stained mouse cardiomyocytes (magnification, ×200). Scale
bar, 50 µm. Brown staining of nuclei indicates apoptotic cells. (B)
Quantification of the apoptotic index of mouse cardiomyocytes,
expressed as apoptotic rate of myocardial cells (%). Data are
expressed as mean ± SD and statistical significance was analyzed by
one-way ANOVA followed by Tukey's post-hoc test. *P<0.05 vs.
Sham group; #P<0.05 vs. AMI group;
∆P<0.05 vs. AMI + BRCC36 group. AMI, acute myocardial
infarction; BRCC36, Lys-63-specific deubiquitinase BRCC36.

Figure 3

Representative histopathology of
myocardial tissue. Photomicrographs (magnification, ×200) of
sections stained with H&E, Masson's trichrome and Sirius red.
Scale bar, 50 µm. Representative histological images are shown;
quantitative analysis of the staining is presented in Fig. 4. AMI, acute myocardial infarction;
BRCC36, Lys-63-specific deubiquitinase BRCC36.

Figure 4

Quantification of myocardial fibrosis
in mice. (A) Area of collagen surrounding the infarct (%),
quantified from Masson's trichrome-stained sections shown in
Fig. 3. (B) Ratio of type I/III
collagen, determined by Sirius red staining under polarized light
from the sections shown in Fig. 3.
Data are presented as mean ± SD and statistical analysis was
performed using one-way ANOVA followed by Tukey's post hoc test.
*P<0.05 vs. sham group; #P<0.05 vs. AMI group;
∆P<0.05 vs. AMI + BRCC36 group. AMI, acute myocardial
infarction; BRCC36, Lys-63-specific deubiquitinase BRCC36.

Figure 5

Protein expression of Wnt/JNK pathway
components in mouse myocardial tissue. (A) Representative western
blotting images for Wnt5a, c-Jun, p-c-Jun, JNK and p-JNK protein
expression in myocardial tissues. (B) Ratio of p-c-Jun to total
c-Jun protein expression. (C) Ratio of p-JNK to total JNK protein
expression. Data are shown as mean ± SD and statistically analyzed
by one-way ANOVA followed by Tukey's post hoc test. *P<0.01 vs.
sham group; #P<0.01 vs. AMI group;
∆P<0.05 vs. AMI + BRCC36 group. AMI, acute myocardial
infarction; BRCC36, Lys-63-specific deubiquitinase BRCC36; p-,
phosphorylated.
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Copy and paste a formatted citation
Spandidos Publications style
Guo Y, Chen L, Li S, Zhang X and Lin H: Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway. Mol Med Rep 33: 140, 2026.
APA
Guo, Y., Chen, L., Li, S., Zhang, X., & Lin, H. (2026). Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway. Molecular Medicine Reports, 33, 140. https://doi.org/10.3892/mmr.2026.13850
MLA
Guo, Y., Chen, L., Li, S., Zhang, X., Lin, H."Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway". Molecular Medicine Reports 33.5 (2026): 140.
Chicago
Guo, Y., Chen, L., Li, S., Zhang, X., Lin, H."Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway". Molecular Medicine Reports 33, no. 5 (2026): 140. https://doi.org/10.3892/mmr.2026.13850
Copy and paste a formatted citation
x
Spandidos Publications style
Guo Y, Chen L, Li S, Zhang X and Lin H: Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway. Mol Med Rep 33: 140, 2026.
APA
Guo, Y., Chen, L., Li, S., Zhang, X., & Lin, H. (2026). Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway. Molecular Medicine Reports, 33, 140. https://doi.org/10.3892/mmr.2026.13850
MLA
Guo, Y., Chen, L., Li, S., Zhang, X., Lin, H."Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway". Molecular Medicine Reports 33.5 (2026): 140.
Chicago
Guo, Y., Chen, L., Li, S., Zhang, X., Lin, H."Mechanism of BRCC36 affecting cardiac rupture after acute infarction through the Wnt‑JNK signaling pathway". Molecular Medicine Reports 33, no. 5 (2026): 140. https://doi.org/10.3892/mmr.2026.13850
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