Mechanism of the Fibroblast Growth Factor 23/α-Klotho Axis in Peripheral Blood Mononuclear Cell Inflammation in Alzheimer’s Disease

ABSTRACT

Alzheimer’s disease (AD) is a prevalent type of dementia and threatens the health of most elderly people and poses a huge burden to families and society. The fibroblast growth factor 23 (FGF23)/α-Klotho axis is associated with multiple aging-related diseases. Hence, this study explored the mechanism of the FGF23/α-Klotho axis in AD. FGF23/α-Klotho protein contents and levels of inflammatory cytokines in AD patients were measured, and the correlation between FGF23/α-Klotho protein contents and inflammatory cytokines was analyzed. FGF23 and α-Klotho expressions were blocked in peripheral blood mononuclear cells (PBMCs) in AD patients (AD-PBMCs) to assess the effects on cell inflammation and the Wnt/β-catenin pathway activation. The Wnt/β-catenin pathway was inhibited to evaluate cell inflammation. Combined treatments of the cells were conducted to verify the role of the FGF23/α-Klotho axis and the Wnt/β-catenin pathway in inflammation in AD-PBMCs. Increased FGF23 protein concentration and reduced α-Klotho protein concentration were observed in AD patients and correlated with inflammatory cytokine levels. FGF23 inhibition or α-Klotho overexpression reduced the production of inflammatory cytokines and activated the Wnt/β-catenin pathway in AD-PBMCs. Blocking the Wnt/β-catenin pathway increased inflammatory cytokine production in AD-PBMCs and annulled the effects of the FGF23/α-Klotho axis on AD-induced cell inflammation. We concluded that the FGF23/α-Klotho axis can regulate the AD-induced cell inflammation through the Wnt/β-catenin pathway.

KEYWORDS:

• Alzheimer’s disease
• fibroblast growth factor 23/α-Klotho
• inflammation
• peripheral blood mononuclear cells
• Wnt/β-catenin

Acknowledgments

We would like to thank all the participants for their time and effort.

Author contributions

BL, MZ, and JP designed the research; QY contributed unpublished reagents; JC and RL performed the research; YJ wrote the paper.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the Medical Science Research Project of Chongqing Health and Family Planning Commission, China [2016MSXM080].