TGF‑β1 in obstructive sleep apnea: linking intermittent hypoxia, upper‑airway remodeling, and systemic comorbidities

Obstructive sleep apnea (OSA) is a common but underdiagnosed disorder associated with cardiometabolic, neurocognitive, and malignant comorbidities. Transforming growth factor-β1 (TGF-β1) is a central profibrotic cytokine and may link OSA exposures to upper-airway remodeling and systemic injury.

To synthesize current evidence implicating TGF-β1 signaling in OSA pathogenesis and comorbidities, and to highlight translational implications and key knowledge gaps.

We conducted a structured literature search in PubMed, Embase, Web of Science, and the Cochrane Library (inception to March 10, 2026) and narratively synthesized English-language original studies in humans and experimental models.

Evidence directly connecting TGF-β1 to human upper-airway remodeling in OSA remains limited and largely observational, whereas intermittent hypoxia(IH) models and non-OSA fibrotic research support plausible mechanisms involving latent TGF-β activation, SMAD/non-SMAD signaling, oxidative stress (e.g., NOX4), and extracellular matrix stiffening. Findings across biological matrices and treatment studies (e.g., continuous positive airway pressure (CPAP) effects on airway vs. circulating markers) are heterogeneous.

TGF-β1 is a mechanistically plausible mediator linking OSA exposures to remodeling and multisystem comorbidities, but OSA-specific causal evidence is insufficient. Future work should prioritize standardized phenotyping, compartment-specific assays (active vs. total TGF-β1), and longitudinal designs integrating treatment response and tissue-level remodeling endpoints.