Interstitial macrophage-derived thrombospondin-1 contributes to hypoxia-induced pulmonary hypertension.

ABSTRACT:

Aims

Transforming growth factor-β (TGF-β) signalling is required for chronic hypoxia-induced pulmonary hypertension (PH). The activation of TGF-β by thrombospondin-1 (TSP-1) contributes to the pathogenesis of hypoxia-induced PH. However, neither the cellular source of pathologic TSP-1 nor the downstream signalling pathway that link activated TGF-β to PH have been determined. In this study, we hypothesized that circulating monocytes, which are recruited to become interstitial macrophages (IMs), are the major source of TSP-1 in hypoxia-exposed mice, and TSP-1 activates TGF-β with increased Rho-kinase signalling, causing vasoconstriction.

Methods and results

Flow cytometry revealed that a specific subset of IMs is the major source of pathologic TSP-1 in hypoxia. Intravenous dep

SUBMITTER: Kumar R 

PROVIDER: S-EPMC7519884 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature