SPHK1-mediated M2 macrophage polarization drives TGF-β1-dependent thrombus fibrosis.

ABSTRACT:

Background and objective

Venous thrombus fibrosis contributes to post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH). M2 macrophages promote fibrosis via TGF-β1 secretion. This study investigates whether sphingosine kinase 1 (SPHK1) promotes thrombus fibrosis by regulating M2 macrophage polarization.

Methods

Histological staining and immunofluorescence (IF) were performed on thrombus tissues from patients with acute thrombosis and CTEPH. Single-cell RNA sequencing (scRNA-seq) was used to characterize immune cell heterogeneity and to identify SPHK1 expression within macrophage subsets. In vivo, a rat model of thrombus was established via inferior vena cava (IVC) ligation, and the SPHK1 inhibitor PF543 was administered to evaluate it

SUBMITTER: Chen X 

PROVIDER: S-EPMC12665702 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature