Histological hallmarks and role of Slug/PIP axis in pulmonary hypertension secondary to pulmonary fibrosis.
Gregoire RuffenachSoban UmarMylene VaillancourtJason HongNancy CaoShervin SarjiShayan MoazeniChristine M CunninghamAbbas ArdehaliSrinivasa T ReddyRajan SaggarGregory FishbeinMansoureh EghbaliPublished in: EMBO molecular medicine (2019)
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.
Keyphrases
- pulmonary hypertension
- end stage renal disease
- epithelial mesenchymal transition
- cell proliferation
- ejection fraction
- newly diagnosed
- transcription factor
- pulmonary artery
- pulmonary fibrosis
- prognostic factors
- extracellular matrix
- chronic kidney disease
- endothelial cells
- peritoneal dialysis
- poor prognosis
- patient reported outcomes
- optical coherence tomography
- signaling pathway
- systemic sclerosis
- binding protein
- case report
- mesenchymal stem cells
- long non coding rna
- single molecule
- idiopathic pulmonary fibrosis
- pluripotent stem cells
- stress induced