CTRP1 Aggravates Cardiac Fibrosis by Regulating The NOX2/P38 Pathway in Macrophages
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 t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2022-12-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | https://www.celljournal.org/article_255122_306c53ed569a5b779f10ac7d23e64b07.pdf |
| Summary: | 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. |
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| ISSN: | 2228-5806 2228-5814 |