FGF23 Controls Myocardial Fibrosis Progression via Promoting Cardiac Fibroblast Proliferation and Activation in Mice

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.