Surreal illustration of a heart transforming into scar tissue, symbolizing FGF23's role in myocardial fibrosis.

Decoding FGF23: How This Hormone Impacts Your Heart Health

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Samir D’Costa in Health & Wellness December 2025 • 5 min read.

"New research uncovers the role of FGF23 in promoting myocardial fibrosis, offering potential targets for future heart disease treatments."


Fibroblast growth factor 23 (FGF23) has traditionally been recognized for its vital role in maintaining phosphate balance and vitamin D metabolism within the body. Produced by bone cells, FGF23 acts on the kidneys and parathyroid glands to ensure these levels stay within a healthy range. However, emerging research is revealing a darker side to this hormone, linking elevated FGF23 levels to various pathological effects, especially concerning heart health.

One significant area of concern is the connection between FGF23 and left ventricular hypertrophy (LVH), a condition where the heart's main pumping chamber thickens, making it harder for the heart to function effectively. Studies have shown that individuals with chronic kidney disease often exhibit markedly elevated FGF23 levels, and this, in turn, can directly contribute to LVH. But the story doesn't end there.

A new study is shedding light on FGF23's potential role in promoting myocardial fibrosis, a condition characterized by the excessive buildup of scar tissue in the heart muscle. This process can stiffen the heart, impair its ability to relax and fill with blood, and ultimately lead to diastolic dysfunction, a type of heart failure. Understanding how FGF23 contributes to myocardial fibrosis could pave the way for novel therapeutic strategies to protect heart health.

How Does FGF23 Promote Heart Fibrosis?

Surreal illustration of a heart transforming into scar tissue, symbolizing FGF23's role in myocardial fibrosis.

To investigate the role of FGF23 in myocardial fibrosis, researchers conducted a series of experiments using both in vitro (cell-based) and in vivo (animal) models. They observed that myocardial and plasma FGF23 levels, as well as levels of FGF receptor 4 (FGFR4), were increased in mice with heart failure. Similar increases were seen in cultured adult mouse cardiac fibroblasts (AMCFs) when exposed to substances like angiotensin II, phenylephrine, and soluble fractalkine – all known to contribute to cardiac stress and remodeling.

Further experiments revealed that recombinant FGF23 protein increased the expression of active β-catenin, procollagen I, and procollagen III in cultured AMCFs. Procollagens I and III are precursors to collagen, the main component of scar tissue. Beta-catenin is a protein involved in cell signaling pathways that can promote fibrosis. These findings suggest that FGF23 may trigger a cascade of events that leads to increased collagen production and ultimately, myocardial fibrosis.

  • Increased FGF23: Elevated levels of FGF23 in heart failure models.
  • Fibroblast Response: Cardiac fibroblasts (AMCFs) show increased FGF23 and FGFR4 when exposed to stress factors.
  • Collagen Production: FGF23 boosts procollagen I and III expression, leading to fibrosis.
  • Beta-Catenin Activation: FGF23 activates β-catenin, a key fibrosis promoter.
To confirm these findings in a living system, the researchers injected mice with adeno-associated virus-FGF23 (AAV-FGF23) to increase FGF23 levels directly in the heart. This resulted in a significant increase in left ventricular end-diastolic pressure (a measure of how well the heart relaxes) and myocardial fibrosis. Furthermore, the expression of active β-catenin, transforming growth factor-β (TGF-β), procollagen I, and procollagen III was markedly upregulated in both myocardial infarction (MI) and ischemia/reperfusion (IR) models. Importantly, inhibiting β-catenin or silencing it through genetic techniques was able to counteract the FGF23-promoted myocardial fibrosis, both in vitro and in vivo.

Looking Ahead: Targeting FGF23 for Heart Health

This research provides compelling evidence that FGF23 plays a significant role in promoting myocardial fibrosis and exacerbating diastolic dysfunction in the context of MI and IR. The key mechanism appears to involve the upregulation of active β-catenin and TGF-β, both of which are known drivers of fibrotic processes. While more research is needed to fully elucidate the intricate details of this pathway, these findings suggest that targeting FGF23 signaling could be a promising therapeutic strategy for preventing or treating myocardial fibrosis and improving heart function. Future studies should focus on developing specific FGF23 inhibitors or β-catenin antagonists that can be safely and effectively used in humans to combat heart disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.18632/oncotarget.11623, Alternate LINK

Title: Fgf23 Promotes Myocardial Fibrosis In Mice Through Activation Of Β-Catenin

Subject: Oncology

Journal: Oncotarget

Publisher: Impact Journals, LLC

Authors: Huixin Hao, Xixian Li, Qingman Li, Hairuo Lin, Zhenhuan Chen, Jiahe Xie, Wanling Xuan, Wangjun Liao, Jianping Bin, Xiaobo Huang, Masafumi Kitakaze, Yulin Liao

Published: 2016-08-25

Everything You Need To Know

1

What is FGF23?

FGF23, or Fibroblast Growth Factor 23, is a hormone mainly recognized for its role in regulating phosphate levels and vitamin D metabolism. It is produced by bone cells and acts on the kidneys and parathyroid glands to maintain these levels within a healthy range. Recent studies suggest it also plays a role in heart health.

2

What is myocardial fibrosis and how is it related?

Myocardial fibrosis is characterized by the excessive buildup of scar tissue in the heart muscle. This process can stiffen the heart, impair its ability to relax and fill with blood, and ultimately lead to diastolic dysfunction, a type of heart failure. The research indicates that FGF23 contributes to this condition, potentially through activation of the β-catenin pathway leading to increased collagen production.

3

Why is FGF23 important in this context?

FGF23's significance lies in its newly discovered association with heart health. Elevated levels of FGF23 have been linked to myocardial fibrosis and left ventricular hypertrophy (LVH), which is a thickening of the heart's main pumping chamber. This implies that FGF23 might be a key player in the development of heart disease, particularly in conditions like myocardial infarction (MI) and ischemia/reperfusion (IR).

4

How does FGF23 promote fibrosis in the heart?

The research suggests that increased FGF23 levels can trigger a cascade that leads to myocardial fibrosis. In experiments, the study showed that FGF23 directly increases the expression of active β-catenin, procollagen I, and procollagen III in cardiac fibroblasts. Procollagens I and III are precursors to collagen, the main component of scar tissue. Beta-catenin is a protein involved in cell signaling pathways that can promote fibrosis. When mice were injected with AAV-FGF23, it resulted in an increase in left ventricular end-diastolic pressure and myocardial fibrosis. Blocking beta-catenin was able to counteract the fibrosis.

5

What is the potential for treating heart conditions related to FGF23?

Future studies could focus on developing specific FGF23 inhibitors or β-catenin antagonists. Targeting the FGF23 signaling pathway could be a promising therapeutic strategy for preventing or treating myocardial fibrosis and improving heart function. This approach aims to counteract the harmful effects of elevated FGF23 levels and protect the heart from damage.

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