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Updated: Apr 30, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
A cardiac fibrosis specific circRNA_006640 sponges miR-7648-3p and miR-185-3p to synergistically up-regulate CTGF
Lijuan Yang1, XiaoMin He2, Kai Luo2
1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, TongJi University, Shanghai, 200092, China.
Abstract:
Cardiac fibrosis is a critical pathological feature in nearly all forms of heart disease and contributes to heart failure. However, existing diagnostic and therapeutic approaches are insufficient for detecting fibrosis or targeting conventional pathways. Further molecular investigations are urgently needed to develop effective treatments. Circular RNAs (circRNAs), distinguished by their stability and regulatory roles, show significant potential. CircRNA_006640 was substantially upregulated in left ventricular tissues of male mice subjected to transverse aortic constriction, as well as in blood samples. Gain- and loss-of-function studies confirmed that circRNA_006640 promoted proliferation and phenotypic transformation in mouse cardiac fibroblasts. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting demonstrated that circRNA_006640 suppressed miR-7648-3p and miR-185-3p, which in turn inhibited connective tissue growth factor (CTGF). Furthermore, there was a synergistic effect between miR-7648-3p and miR-185-3p to enhance the suppression of CTGF. In vivo, circRNA_006640 markedly exacerbated cardiac fibrosis. Knockdown of circRNA_006640 using small interfering RNA effectively mitigated cardiac fibrosis and preserved cardiac function, indicating therapeutic potential for antifibrotic strategies. CircRNA_006640 acts as a novel upstream regulator of CTGF, exacerbating cardiac fibrosis by sponging miR-7648-3p and miR-185-3p. The synergistic interaction between miR-7648-3p and miR-185-3p strengthens the profibrotic effect. Targeting CircRNA_006640 may hold promising therapeutic potential for cardiac fibrosis.
Insights
Circular RNA_006640 promotes cardiac fibrosis by suppressing microRNAs that inhibit CTGF. Targeting this circular RNA offers a potential therapeutic strategy for heart disease.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- RNA Biology
Background:
- Cardiac fibrosis is a key factor in heart failure, with limited diagnostic and therapeutic options.
- Circular RNAs (circRNAs) are stable molecules with regulatory roles, showing potential in disease pathology.
- Novel molecular targets are needed for effective antifibrotic therapies.
Purpose of the Study:
- To investigate the role of circRNA_006640 in cardiac fibrosis.
- To elucidate the molecular mechanism underlying circRNA_006640's function in cardiac fibroblasts.
- To evaluate circRNA_006640 as a potential therapeutic target for cardiac fibrosis.
Main Methods:
- Transverse aortic constriction in mice to induce cardiac fibrosis.
- Gain- and loss-of-function studies in mouse cardiac fibroblasts.
- Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting.
- In vivo knockdown of circRNA_006640 using small interfering RNA (siRNA).
Main Results:
- CircRNA_006640 was upregulated in cardiac tissues and blood following transverse aortic constriction.
- CircRNA_006640 promoted cardiac fibroblast proliferation and phenotypic transformation.
- CircRNA_006640 suppressed miR-7648-3p and miR-185-3p, leading to increased connective tissue growth factor (CTGF) expression.
- Synergistic inhibition of CTGF by miR-7648-3p and miR-185-3p was observed.
- In vivo knockdown of circRNA_006640 attenuated cardiac fibrosis and preserved cardiac function.
Conclusions:
- CircRNA_006640 acts as a novel upstream regulator of CTGF, exacerbating cardiac fibrosis.
- The mechanism involves sponging of miR-7648-3p and miR-185-3p, with synergistic effects enhancing profibrotic activity.
- Targeting circRNA_006640 presents a promising therapeutic strategy for antifibrotic interventions in heart disease.
