# PLSCR1 Regulates the Physiology of Fibroblast‐Like Synoviocytes via Modulating the STAT1 Signaling Pathway

## TL;DR

PLSCR1 is increased in rheumatoid arthritis and affects joint cells by controlling the STAT1 pathway, suggesting it could be a new treatment target.

## Contribution

This study reveals a novel regulatory role of PLSCR1 in RA through modulation of the STAT1 signaling pathway in fibroblast-like synoviocytes.

## Key findings

- PLSCR1 is significantly upregulated in the serum of rheumatoid arthritis patients.
- PLSCR1 knockdown reduces synoviocyte proliferation and inflammation while increasing apoptosis.
- STAT1 activation reverses the effects of PLSCR1 silencing, confirming its regulatory role.

## Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Elucidating the molecular mechanisms underlying the pathogenesis is crucial for identifying novel therapeutic targets. Phospholipid scramblase 1 (PLSCR1) has been implicated in systemic autoimmune diseases. However, the function and underlying mechanism in RA remains unclear.

Reverse transcriptase‐quantitative polymerase chain reaction was used to detect the expression levels of PLSCR1 in the serum of 30 RA patients and 30 healthy controls. The function of PLSCR1 in human fibroblast‐like synoviocytes (HFLSs) was investigated by siRNA‐mediated knockdown. Cell proliferation, apoptosis, and inflammatory cytokine production were assessed through 5‐ethynyl‐2'‐deoxyuridine (EdU) assays, flow cytometry and enzyme‐linked immunosorbent assays. The regulatory relationship between PLSCR1 and signal transducer and activator of transcription 1 (STAT1) was further explored using 2‐NP rescue experiments.

PLSCR1 was significantly upregulated in the serum of RA patients. Silencing PLSCR1 in HFLSs led to decreased proliferation, increased apoptosis, reduced levels of tumor necrosis factor alpha, interleukin‐1‐beta, and IL‐6, and downregulation of STAT1 expression. Notably, activation of STAT1 signaling reversed the effects of PLSCR1 knockdown, restoring proliferative capacity and inflammatory cytokine production while reducing apoptosis.

PLSCR1 is upregulated in RA and regulates the proliferation, apoptosis and inflammation of FLSs by modulating the STAT1 signaling pathway. These findings suggest that PLSCR1 may serve as a potential molecular target for RA therapy.