The regulation of placental pericyte function through transforming growth factor β-1 signalling.

In the placenta, fetal-derived pericytes wrap the villous capillaries, directly interacting with endothelial cells to orchestrate the branching angiogenesis required to meet the demands of the growing fetus. In animal models of preeclampsia (PE), there is a positive correlation between reduced αSMA-expressing pericyte coverage and reduced vascular branching. Transforming Growth Factor β-1 (TGFβ-1) signalling is critical to placental development, is altered in placental pathology and alters pericyte function in other organs. However, the factors that influence placental pericyte function are under-investigated. In the present study, we investigated the in vitro effects of TGFβ-1 signalling on the population dynamics and functional measures of isolated term human placental pericytes, including angiogenic and inflammatory secretions, extracellular matrix (ECM) production, and phagocytic capacity. TGFβ-1 treatment promoted a proangiogenic phenotype with increased pro-angiogenic secretion of VEGFA and MMP-2 and reduced vessel stabilizing secretion of (ANG-1), without affecting the production of ECM components. Pericyte secretion of inflammation-associated adhesion molecule sVCAM-1, cytokine IL-6, chemokine MCP-1, and their phagocytosis capacity were attenuated with TGFβ-1 treatment. While some effects were mediated via the type I receptor ALK5, others were not, suggesting that TGFβ-1 signalling in placental pericytes may additionally occur via ALK1. Thus, it is likely that locally secreted TGFβ-1, contributes to the regulation of villous pericyte properties and their barrier function, and may implicate dysregulated TGFβ-1 signalling as a mechanism for the compromised placental fetal vascular branching observed in many placental pathologies. These findings are timely with emerging evidence that TGFβ is involved in the pathogenesis of PE.