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Updated: Apr 14, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
FGF23 Controls Myocardial Fibrosis Progression via Promoting Cardiac Fibroblast Proliferation and Activation in Mice
Leyi Shen1, Mingqi Hu1, Mei Xue1
1School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China.
Insights
Fibroblast Growth Factor 23 (FGF23) significantly contributes to cardiac fibrosis in heart failure (HF). Inhibiting FGF23 alleviates fibrosis, suggesting FGF23 as a potential therapeutic target for HF treatment.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Fibrosis Research
Background:
- Heart failure (HF) is a major global health concern.
- Myocardial fibrosis is a key factor worsening ventricular dysfunction in HF.
Purpose of the Study:
- To investigate the role of Fibroblast Growth Factor 23 (FGF23) in cardiac fibrosis associated with HF.
- To explore FGF23 as a potential therapeutic target for HF and cardiac fibrosis.
Main Methods:
- Utilized a mouse model of transverse aortic constriction (TAC) to induce cardiac fibrosis.
- Administered FGF23 monoclonal antibody for inhibition and recombinant FGF23 (rFGF23) protein for exacerbation.
- Performed RNA sequencing and analyzed fibroblast proliferation markers (Ki67, Cyclin D1, Cyclin E1, PCNA, α-SMA, collagen 1A1) in vitro.
- Investigated the involvement of FGFR4 and MAPK/ERK signaling pathways.
Main Results:
- FGF23 was upregulated in fibrotic mouse hearts post-TAC.
- FGF23 inhibition ameliorated TAC-induced cardiac fibrosis; rFGF23 exacerbated it.
- rFGF23 treatment increased cardiac fibroblast proliferation and activation markers.
- FGF23 promotes fibroblast proliferation via FGFR4 and MAPK/ERK signaling.
Conclusions:
- FGF23 plays a significant role in regulating myocardial fibrosis in HF.
- Targeting FGF23 presents a promising therapeutic strategy for treating HF and cardiac fibrosis.
Abstract:
Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin D metabolism, was significantly upregulated in fibrotic mouse hearts after transverse aortic constriction (TAC). By using the FGF23 monoclonal antibody, we found that inhibition of FGF23 alleviated TAC-induced cardiac fibrosis, while injection of recombinant FGF23 (rFGF23) protein exacerbated tissue fibrosis in mouse hearts after TAC. RNA sequencing indicated that FGF23 may promote cardiac fibroblast proliferation and activation in stressed mouse hearts. In human primary cardiac fibroblasts, rFGF23 treatment further upregulated the expression of Ki67, Cyclin D1, Cyclin E1, PCNA, α-SMA, and collagen 1A1 after TGF-β stimulation. Further results indicated that FGF23 promoted cardiac fibroblast proliferation and activation through FGFR4 and activated the downstream MAPK/ERK signaling. This study suggests a role of FGF23 in the regulation of myocardial fibrosis, which shows the potential of targeting FGF23 in the treatment of HF and cardiac fibrosis.
