Histological hallmarks and role of Slug/PIP axis in pulmonary hypertension secondary to pulmonary fibrosis
Abstract Pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF‐PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly under...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201810061 |
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| Summary: | Abstract Pulmonary hypertension secondary to pulmonary fibrosis (PF‐PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF‐PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non‐fibrotic areas of PF‐PH patient lungs compared to PF patients. The increased vascular wall thickness in PF‐PH patients is concomitant with a significantly increased expression of the transcription factor Slug within the macrophages and its target prolactin‐induced protein (PIP), an extracellular matrix protein that induces pulmonary arterial smooth muscle cell proliferation. We developed a novel translational rat model of combined PF‐PH that is reproducible and shares similar histological features (fibrosis, pulmonary vascular remodeling) and molecular features (Slug and PIP upregulation) with human PF‐PH. We found Slug inhibition decreases PH severity in our animal model of PF‐PH. Our study highlights the role of Slug/PIP axis in PF‐PH. |
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| ISSN: | 1757-4676 1757-4684 |