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Review
. 2023 Mar 17:14:1135384.
doi: 10.3389/fimmu.2023.1135384. eCollection 2023.

Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis

Zihan Wang  1   2 , Jinping Wang  1 , Tianyi Lan  2 , Liubo Zhang  2 , Zeran Yan  1 , Nan Zhang  1 , Yuan Xu  1 , Qingwen Tao  1
Affiliations
Review

Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis

Zihan Wang et al. Front Immunol. .

Abstract

Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP and play important roles in regulating the cellular immune, inflammatory, invasion, migration, proliferation, and angiogenesis responses in the synovial region. Overexpression of FAP is regulated by the initial inflammatory microenvironment of the disease and epigenetic signaling, which promotes RA development by regulating FLSs or affecting the signaling cross-linking FLSs with other cells at the local synovium and inflammatory stimulation. At present, several treatment options targeting FAP are in the process of development. This review discusses the basic features of FAP expressed on the surface of FLSs and its role in RA pathophysiology and advances in targeted therapies.

Keywords: cell function; fibroblast-activated protein-α; fibroblast-like synoviocytes; rheumatoid arthritis; targeted therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The synovial joint in health and in RA. (A) In healthy joints, the synovial tissue is sparse, with only one or two layers of cells. (B) In RA, synovial cells proliferate and become invasive, causing cartilage and bone to erode. (C) Surface markers of FLSs and their main locations.
Figure 2
Figure 2
A Schematic view of cellular functions of FAP-mediated FLSs in RA. Arrows (↓) indicate positive impact, while inverted Ts (⊥) indicate negative impact. The dotted arrows (—) indicate studies that exist but have not yet been validated in the RA field.
See this image and copyright information in PMC

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Grants and funding

This study received funding support from the Beijing Natural Science Foundation (7232319) and National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-02-02; 2022-NHLHCRF-LX-02-0105; 2022-NHLHCRF-LX-02-0103).