PMID- 37434456 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230718 IS - 2228-5806 (Print) IS - 2228-5814 (Electronic) IS - 2228-5806 (Linking) VI - 25 IP - 6 DP - 2023 Jun 28 TI - Peroxiredoxin 3 Inhibits Cardiac Fibrosis in Mice via NOX4-P38 Signalling. PG - 391-398 LID - 704470 [pii] LID - 10.22074/cellj.2023.557603.1082 [doi] AB - 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 beta1 (TGFbeta1) 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. FAU - Xiong, Xiaoqi AU - Xiong X AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Li, Jun AU - Li J AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Chen, Zhen AU - Chen Z AD - Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, P.R. China. FAU - Luo, Changjun AU - Luo C AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Wei, Wei AU - Wei W AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Li, Bing AU - Li B AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Kang, Yi AU - Kang Y AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Nong, Xiuhong AU - Nong X AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. FAU - Ai, Fen AU - Ai F AD - Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, P.R. China. Email: wtt20220520@126.com. FAU - Zhang, Jing AU - Zhang J AD - Department of Cardiology, Liuzhou Municipal Liutie Central Hospital, Liuzhou City, Guang Xi Province, P.R. China. Email: abc20220427@126.com. LA - eng PT - Journal Article DEP - 20230628 PL - Iran TA - Cell J JT - Cell journal JID - 101566618 PMC - PMC10331444 OTO - NOTNLM OT - Cardiac fibrosis OT - Isoproterenol OT - NADPH Oxidase 4 OT - P38 OT - Peroxiredoxin 3 EDAT- 2023/07/12 06:42 MHDA- 2023/07/12 06:43 PMCR- 2023/06/01 CRDT- 2023/07/12 02:43 PHST- 2022/07/11 00:00 [received] PHST- 2023/07/12 06:43 [medline] PHST- 2023/07/12 06:42 [pubmed] PHST- 2023/07/12 02:43 [entrez] PHST- 2023/06/01 00:00 [pmc-release] AID - 704470 [pii] AID - 10.22074/cellj.2023.557603.1082 [doi] PST - epublish SO - Cell J. 2023 Jun 28;25(6):391-398. doi: 10.22074/cellj.2023.557603.1082.