Peroxiredoxin 3 Inhibits Cardiac Fibrosis in Mice via NOX4-P38 Signalling

Document Type : Original Article

Authors

1 Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China

2 Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, P.R. China

Abstract

Objective: Peroxiredoxin-3 (Prx-3) is widely acknowledged as an antioxidant that protects against mitochondrial
reactive oxygen species. Nonetheless, its role in cardiac fibrosis has not been elucidated. We aim to explore the role
and mechanism of Prx-3 in cardiac fibrosis.

Materials and Methods: In this experimental study, mice received subcutaneous injections of isoproterenol (ISO) for 14
consecutive days (10 mg/kg/d for three days, followed by 5 mg/kg/d for 11 days) to establish a cardiac fibrosis model. The
mice were subsequently injected with adenovirus-Prx-3 (ad-Prx-3) to enable Prx-3 overexpression. Echocardiography
was used to evaluate cardiac function. Mice heart fibroblasts were isolated and stimulated with transforming growth
factor β1 (TGFβ1) to induce fibrosis in vitro. Cells were also transfected with ad-Prx-3 for overexpression of Prx-3.

Results: Echocardiographic diameters and fibrosis markers indicated that Prx-3 could inhibit ISO-induced cardiac
dysfunction and fibrosis. Fibroblasts with Prx-3 overexpression exhibited reduced activation, proliferation, and collagen
transcription. We found that Prx-3 reduced the expression of NADPH oxidase 4 (NOX4) and reduced P38 levels. After
treatment with a P38 inhibitor, the Prx-3 overexpression-induced anti-fibrosis effect was mitigated.
Conclusion: Prx-3 could protect against ISO-induced cardiac fibrosis by inhibiting the NOX4-P38 pathway.

Keywords

Main Subjects

References

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Cell Journal (Yakhteh)
Volume 25, Issue 6
June 2023
Pages 391-398

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