# The JAK1-STAT1 signaling pathway triggers inflammation responses in chronic obstructive sleep apnea rat model

## TL;DR

This study shows that the JAK1-STAT1 pathway is involved in inflammation caused by chronic obstructive sleep apnea in rats, and blocking JAK1 may help reduce this inflammation.

## Contribution

The study identifies JAK1-STAT1 signaling as a key driver of inflammation in chronic obstructive sleep apnea and demonstrates the therapeutic potential of JAK1 inhibition.

## Key findings

- CIH increased serum IL-6 and TNF-α levels and activated lung p-JAK1/p-STAT1.
- Filgotinib reduced inflammation markers, suppressed JAK1-STAT1 activation, and improved airway resistance.
- Lung p-STAT1 strongly correlated with serum IL-6 and TNF-α levels.

## Abstract

Chronic obstructive sleep apnea (OSA) drives systemic inflammation; the role of the JAK1-STAT1 pathway is unclear.

To elucidate JAK1-STAT1 involvement in OSA-related inflammation using a chronic intermittent hypoxia (CIH) model.

Sprague-Dawley rats underwent 8-week CIH (FiO₂ cycling 5–21%, 8h/day) or normoxia (Sham). Serum cytokines (ELISA) and lung p-JAK1/p-STAT1 (Western blot/IHC) were analyzed. A CIH subset received JAK1 inhibitor filgotinib. Airway resistance was assessed via forced oscillation.

CIH elevated serum IL-6/TNF-α versus Sham (p < 0.05) and increased lung p-JAK1/p-STAT1. Filgotinib reduced cytokines, suppressed p-JAK1/p-STAT1, attenuated leukocyte infiltration/collagen deposition, and improved airway resistance. Lung p-STAT1 strongly correlated with serum IL-6 (r = 0.86) and TNF-α (r = 0.82) (both p < 0.001).

JAK1-STAT1 signaling critically mediates CIH-induced inflammation. JAK1 inhibition attenuates inflammatory responses, demonstrating therapeutic potential for OSA comorbidities.