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CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38 Pathway in Macrophages

Authors :
Chenyu Li
Shaozhen Ying
Xiaolin Wu
Tongjian Zhu
Qing Zhou
Yue Zhang
Yongsheng Liu
Rui Zhu
He Hu
Source :
Cell Journal, Vol 24, Iss 12, Pp 732-740 (2022)
Publication Year :
2022
Publisher :
Royan Institute (ACECR), Tehran, 2022.

Abstract

ObjectiveC1q/TNF-related proteins 1 (CTRP1) is a recently identified adiponectin associated with obesity-linked disorders and adverse cardiovascular events. The effect of CTRP1 on cardiac fibrosis has not yet been fully elucidated; thus, we aimed to explore this association.Materials and MethodsIn this experimental study, a mouse model of cardiac fibrosis was established by administeringisoproterenol (ISO) (subcutaneously injecting 10 mg/kg/day for 3 days and then 5 mg/kg/day for 11 days). Mice were also injected with recombinant CTRP1 protein (200 μg/kg) 14 days after the final ISO administration. Adult mouse fibroblasts were isolated and stimulated with transforming growth factor (TGF) β1, followed by treatment with recombinant CTRP1. Primary bone marrow-derived macrophages were isolated from C57BL/6J mice and treated with recombinant CTRP1 as well.ResultsCTRP1 level was increased in mouse plasma and heart tissue 2 weeks after ISO injection. Our findingsindicated that recombinant CTRP1 injection aggravated ISO-induced cardiac fibrosis and dysfunction. However,recombinant CTRP1 did not alter TGFβ1-induced fibroblast proliferation and activation or collagen transcription.Recombinant CTRP1 exacerbated ISO-induced macrophage infiltration and inflammatory response. We determinedthat macrophages treated with recombinant CTRP1 showed increased pro-inflammatory cytokine release. Fibroblastsco-cultured with macrophages treated with recombinant CTRP1 showed increased proliferation and collagentranscription. We also found that CTRP1 upregulated the NADPH oxidase 2 (NOX2)/p38 pathway in macrophages.When we inhibited p38 signaling, the pro-inflammatory effect of CTRP1 on macrophages was counteracted. Fibroblastsco-cultured with macrophages treated with a p38 inhibitor also showed limited proliferation and collagen transcription.Conclusion: Cardiac fibrosis was aggravated with the activation of the NOX2/p38 pathway in macrophages afterCTRP1 treatment.

Details

Language :
English
ISSN :
22285806 and 22285814
Volume :
24
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Cell Journal
Publication Type :
Academic Journal
Accession number :
edsdoj.9ddd057211ab4fc4914bb8801711ee40
Document Type :
article
Full Text :
https://doi.org/10.22074/cellj.2022.557327.1043