Now showing 1 - 2 of 2
  • Publication
    Transcriptomics and proteomics revealed sex differences in human pulmonary microvascular endothelial cells
    Marked sexual dimorphism is displayed in the onset and progression of pulmonary hypertension (PH). Females more commonly develop pulmonary arterial hypertension (PAH), yet females with PAH and other types of PH have better survival than males. Pulmonary microvascular endothelial cells play a crucial role in the pulmonary vascular remodelling and increased pulmonary vascular resistance in PH. Given this background, we hypothesized that there are sex differences in the pulmonary microvascular endothelium basally and in response to hypoxia that are independent of the sex hormone environment. Human pulmonary microvascular endothelial cells (HPMECs) from healthy male and female donors, cultured under physiological shear stress, were analysed using RNA sequencing and label-free quantitative proteomics. Gene set enrichment analysis identified a number of sex different pathways both in normoxia and hypoxia, including pathways that regulate cell proliferation. In vitro, rate of proliferation in female HPMECs was lower than in male HPMECs, a finding that supports the omics results. Interestingly, thrombospondin1, an inhibitor of proliferation, was more highly expressed in female than in male cells. These results demonstrate for the first time important differences between female and male HPMECs that persist in the absence of sex hormone differences and identify novel pathways for further investigation that may contribute to sexual dimorphism in pulmonary hypertensive diseases.
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  • Publication
    Gremlin 1 is required for macrophage M2 polarization
    Pro-proliferative, M2-like polarization of macrophages is a critical step in the development of fibrosis and remodeling in chronic lung diseases such as pulmonary fibrosis and pulmonary hypertension. Macrophages in healthy and diseased lungs express gremlin 1 (Grem1), a secreted glycoprotein that acts in both paracrine and autocrine manners to modulate cellular function. Increased Grem1 expression plays a central role in pulmonary fibrosis and remodeling, however, the role of Grem1 in M2-like polarization of macrophages has not previously been explored. The results reported here show that recombinant Grem1 potentiated M2-like polarization of mouse macrophages and bone marrow-derived macrophages (BMDMs) in response to the Th2 cytokines IL4 and IL13. Genetic depletion of Grem1 in BMDMs inhibited M2 polarization while exogenous gremlin 1 could partially rescue this effect. Taken together, these findings reveal that gremlin 1 is required for M2-like polarization of macrophages. We show here that gremlin 1 potentiated M2 polarization of mouse bone marrow-derived macrophages (BMDMs) in response to the Th2 cytokines IL4 and IL13. Genetic depletion of Grem1 in BMDMs inhibited M2 polarization while exogenous gremlin 1 partially rescued this effect. Taken together, these findings reveal a previously unknown requirement for gremlin 1 in M2 polarization of macrophages and suggest a novel cellular mechanism promoting fibrosis and remodeling in lung diseases.
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