# The dual role of thrombospondin-1 in inflammatory regulation during acute respiratory distress syndrome: a mini-review

## TL;DR

Thrombospondin-1 (Thbs1) has both protective and harmful roles in inflammation during acute respiratory distress syndrome, depending on the context.

## Contribution

This mini-review highlights Thbs1's dual role in ARDS, emphasizing its context-dependent regulation of inflammation and disease progression.

## Key findings

- Thbs1 protects against pulmonary damage in ARDS via ECM protection and TGF-β-dependent repair.
- Dysregulated Thbs1 may worsen ARDS by promoting inflammation and fibrosis.
- Mechanistic insights reveal Thbs1's influence on ECM remodeling and serine protease inhibition.

## Abstract

Inflammation serves as a fundamental defense against tissue injury and infection, yet dysregulation can lead to pathological outcomes. Thrombospondin-1 (Thbs1/TSP1), a multifunctional glycoprotein significantly upregulated during inflammation, exemplifies a dualistic regulator with context-dependent roles. Through modulation of cytokine networks and inflammatory cell activity (notably macrophages), Thbs1 critically governs inflammatory responses. Acute respiratory distress syndrome (ARDS), a life-threatening condition fueled by systemic inflammation secondary to infection or trauma, presents complex pathophysiology requiring elucidation. COVID-19 research highlights elevated Thbs1 expression in severe patients, where it demonstrates protective effects against pulmonary damage primarily via extracellular matrix protection, inhibition of neutrophil serine proteases, and TGF-β-dependent repair pathways. However, paradoxical evidence indicates that dysregulated Thbs1 can also contribute to ARDS pathogenesis, potentially by amplifying inflammation, promoting thromboinflammation, or driving fibrosis. Mechanistic insights reveal Thbs1’s influence on ARDS progression through ECM remodeling, serine protease inhibition, and TGF-β activation. While significant progress has been made in understanding Thbs1 signaling, the precise mechanisms dictating its context-dependent switch between protective and pathogenic functions in inflammatory pathways remain a critical area for future investigation.